Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
July-2021 Volume 59 Issue 1

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2021 Volume 59 Issue 1

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review)

  • Authors:
    • Jing Jin
    • Florina Grigore
    • Clark C. Chen
    • Ming Li
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA
  • Article Number: 45
    |
    Published online on: May 19, 2021
       https://doi.org/10.3892/ijo.2021.5225
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Glioblastoma multiforme (GBM) is a primary brain tumor with a high mortality rate and a median survival time of ~14 months from the initial diagnosis. Although progress has been made in the currently available therapies, the treatment of GBM remains palliative. GBM contains subsets of GBM stem cells (GSCs) that share numerous neural stem/progenitor cell characteristics, such as expression of stem cell markers, self‑renewal and multi‑lineage differentiation capacity, thus contributing to the heterogeneity and complexity of these tumors. GSCs are potentially associated with tumor initiation and they are considered as the driving force behind tumor formation, as they possess tumor‑propagating potential and exhibit preferential resistance to radiotherapy and chemotherapy. Targeting self‑renewal signaling pathways in cancer stem cells may effectively reduce tumor recurrence and significantly improve prognosis. The aim of the present review was to summarize the current knowledge on the self‑renewal signaling pathways of GSCs and discuss potential future targeting strategies for the design of differentiation therapies.
View Figures

Figure 1

View References

1 

Prager BC, Bhargava S, Mahadev V, Hubert CG and Rich JN: Glioblastoma Stem Cells: Driving Resilience through Chaos. Trends Cancer. 6:223–235. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Weller M, Cloughesy T, Perry JR and Wick W: Standards of care for treatment of recurrent glioblastoma - are we there yet? Neuro Oncol. 15:4–27. 2013. View Article : Google Scholar

3 

Jordan CT: Cancer stem cells: Controversial or just misunderstood? Cell Stem Cell. 4:203–205. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Kondo T, Setoguchi T and Taga T: Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 101:781–786. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Choi SA, Lee JY, Phi JH, Wang KC, Park CK, Park SH and Kim SK: Identification of brain tumour initiating cells using the stem cell marker aldehyde dehydrogenase. Eur J Cancer. 50:137–149. 2014. View Article : Google Scholar

6 

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD and Dirks PB: Identification of human brain tumour initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F and Vescovi A: Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 64:7011–7021. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Li Z, Wang H, Eyler CE, Hjelmeland AB and Rich JN: Turning cancer stem cells inside out: An exploration of glioma stem cell signaling pathways. J Biol Chem. 284:16705–16709. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Cheng L, Wu Q, Guryanova OA, Huang Z, Huang Q, Rich JN and Bao S: Elevated invasive potential of glioblastoma stem cells. Biochem Biophys Res Commun. 406:643–648. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Folkins C, Shaked Y, Man S, Tang T, Lee CR, Zhu Z, Hoffman RM and Kerbel RS: Glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal-derived factor 1. Cancer Res. 69:7243–7251. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD and Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Liu Z, Bandyopadhyay A, Nichols RW, Wang L, Hinck AP, Wang S and Sun LZ: Blockade of Autocrine TGF-β signaling inhibits stem cell phenotype, survival, and metastasis of murine breast cancer cells. J Stem Cell Res Ther. 2:1–8. 2012. View Article : Google Scholar

13 

Xi Q, Wang Z, Zaromytidou AI, Zhang XH, Chow-Tsang LF, Liu JX, Kim H, Barlas A, Manova-Todorova K, Kaartinen V, et al: A poised chromatin platform for TGF-β access to master regulators. Cell. 147:1511–1524. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Massagué J: How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 1:169–178. 2000. View Article : Google Scholar

16 

Oshimori N and Fuchs E: The harmonies played by TGF-β in stem cell biology. Cell Stem Cell. 11:751–764. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Liang Y, Zhu F, Zhang H, Chen D, Zhang X, Gao Q and Li Y: Conditional ablation of TGF-β signaling inhibits tumor progression and invasion in an induced mouse bladder cancer model. Sci Rep. 6:294792016. View Article : Google Scholar

18 

Furuta Y, Piston DW and Hogan BL: Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development. 124:2203–2212. 1997. View Article : Google Scholar : PubMed/NCBI

19 

Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis YI and Knaus P: Bone morphogenetic protein receptor complexes on the surface of live cells: A new oligomerization mode for serine/threonine kinase receptors. Mol Biol Cell. 11:1023–1035. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Lee SJ: Identification of a novel member (GDF-1) of the transforming growth factor-beta superfamily. Mol Endocrinol. 4:1034–1040. 1990. View Article : Google Scholar : PubMed/NCBI

21 

McPherron AC and Lee SJ: GDF-3 and GDF-9: Two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J Biol Chem. 268:3444–3449. 1993. View Article : Google Scholar : PubMed/NCBI

22 

Rider CC and Mulloy B: Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists. Biochem J. 429:1–12. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Chirasani SR, Sternjak A, Wend P, Momma S, Campos B, Herrmann IM, Graf D, Mitsiadis T, Herold-Mende C, Besser D, et al: Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells. Brain. 133:1961–1972. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, Brem H, Olivi A, Dimeco F and Vescovi AL: Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 444:761–765. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Raja E, Komuro A, Tanabe R, Sakai S, Ino Y, Saito N, Todo T, Morikawa M, Aburatani H, Koinuma D, et al: Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells. Oncogene. 36:4963–4974. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Tso JL, Yang S, Menjivar JC, Yamada K, Zhang Y, Hong I, Bui Y, Stream A, McBride WH, Liau LM, et al: Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide. Mol Cancer. 14:1892015. View Article : Google Scholar : PubMed/NCBI

27 

Lee J, Son MJ, Woolard K, Donin NM, Li A, Cheng CH, Kotliarova S, Kotliarov Y, Walling J, Ahn S, et al: Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells. Cancer Cell. 13:69–80. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Namkoong H, Shin SM, Kim HK, Ha SA, Cho GW, Hur SY, Kim TE and Kim JW: The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein. BMC Cancer. 6:742006. View Article : Google Scholar : PubMed/NCBI

29 

Yan K, Wu Q, Yan DH, Lee CH, Rahim N, Tritschler I, DeVecchio J, Kalady MF, Hjelmeland AB and Rich JN: Glioma cancer stem cells secrete Gremlin1 to promote their maintenance within the tumor hierarchy. Genes Dev. 28:1085–1100. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Tate CM, Pallini R, Ricci-Vitiani L, Dowless M, Shiyanova T, D'Alessandris GQ, Morgante L, Giannetti S, Larocca LM, di Martino S, et al: A BMP7 variant inhibits the tumorigenic potential of glioblastoma stem-like cells. Cell Death Differ. 19:1644–1654. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Bruna A, Darken RS, Rojo F, Ocaña A, Peñuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J, et al: High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 11:147–160. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Peñuelas S, Anido J, Prieto-Sánchez RM, Folch G, Barba I, Cuartas I, García-Dorado D, Poca MA, Sahuquillo J, Baselga J, et al: TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell. 15:315–327. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Yang HW, Menon LG, Black PM, Carroll RS and Johnson MD: SNAI2/Slug promotes growth and invasion in human gliomas. BMC Cancer. 10:3012010. View Article : Google Scholar : PubMed/NCBI

34 

Savary K, Caglayan D, Caja L, Tzavlaki K, Bin Nayeem S, Bergström T, Jiang Y, Uhrbom L, Forsberg-Nilsson K, Westermark B, et al: Snail depletes the tumorigenic potential of glioblastoma. Oncogene. 32:5409–5420. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Caja L, Tzavlaki K, Dadras MS, Tan EJ, Hatem G, Maturi NP, Morén A, Wik L, Watanabe Y, Savary K, et al: Snail regulates BMP and TGFβ pathways to control the differentiation status of glioma-initiating cells. Oncogene. 37:2515–2531. 2018. View Article : Google Scholar : PubMed/NCBI

36 

Teh JL and Chen S: Glutamatergic signaling in cellular transformation. Pigment Cell Melanoma Res. 25:331–342. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Ghosh D, Ulasov IV, Chen L, Harkins LE, Wallenborg K, Hothi P, Rostad S, Hood L and Cobbs CS: TGFβ-responsive HMOX1 expression is associated with stemness and invasion in glioblastoma multiforme. Stem Cells. 34:2276–2289. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Han W, Xin Z, Zhao Z, Bao W, Lin X, Yin B, Zhao J, Yuan J, Qiang B and Peng X: RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3. J Clin Invest. 123:2103–2118. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Han W, Hu P, Wu F, Wang S, Hu Y, Li S, Jiang T, Qiang B and Peng X: FHL3 links cell growth and self-renewal by modulating SOX4 in glioma. Cell Death Differ. 26:796–811. 2019. View Article : Google Scholar :

40 

Bulstrode H, Johnstone E, Marques-Torrejon MA, Ferguson KM, Bressan RB, Blin C, Grant V, Gogolok S, Gangoso E, Gagrica S, et al: Elevated FOXG1 and SOX2 in glioblastoma enforces neural stem cell identity through transcriptional control of cell cycle and epigenetic regulators. Genes Dev. 31:757–773. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Artavanis-Tsakonas S, Rand MD and Lake RJ: Notch signaling: Cell fate control and signal integration in development. Science. 284:770–776. 1999. View Article : Google Scholar : PubMed/NCBI

42 

Blaumueller CM, Qi H, Zagouras P and Artavanis-Tsakonas S: Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 90:281–291. 1997. View Article : Google Scholar : PubMed/NCBI

43 

Stockhausen MT, Kristoffersen K and Poulsen HS: The functional role of Notch signaling in human gliomas. Neuro Oncol. 12:199–211. 2010. View Article : Google Scholar : PubMed/NCBI

44 

Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R and McKay RD: Notch signalling regulates stem cell numbers in vitro and in vivo. Nature. 442:823–826. 2006. View Article : Google Scholar : PubMed/NCBI

45 

Guichet PO, Guelfi S, Teigell M, Hoppe L, Bakalara N, Bauchet L, Duffau H, Lamszus K, Rothhut B and Hugnot JP: Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells. Stem Cells. 33:21–34. 2015. View Article : Google Scholar

46 

Kanamori M, Kawaguchi T, Nigro JM, Feuerstein BG, Berger MS, Miele L and Pieper RO: Contribution of Notch signaling activation to human glioblastoma multiforme. J Neurosurg. 106:417–427. 2007. View Article : Google Scholar : PubMed/NCBI

47 

Chowdhury S and Sarkar RR: Exploring Notch pathway to elucidate phenotypic plasticity and intra-tumor heterogeneity in fliomas. Sci Rep. 9:94882019. View Article : Google Scholar

48 

Basak O, Giachino C, Fiorini E, Macdonald HR and Taylor V: Neurogenic subventricular zone stem/progenitor cells are Notch1-dependent in their active but not quiescent state. J Neurosci. 32:5654–5666. 2012. View Article : Google Scholar : PubMed/NCBI

49 

Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, et al: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 344:1396–1401. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Ge W, Martinowich K, Wu X, He F, Miyamoto A, Fan G, Weinmaster G and Sun YE: Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation. J Neurosci Res. 69:848–860. 2002. View Article : Google Scholar : PubMed/NCBI

51 

Bansod S, Kageyama R and Ohtsuka T: Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development. Development. 144:3156–3167. 2017. View Article : Google Scholar : PubMed/NCBI

52 

Armesilla-Diaz A, Bragado P, Del Valle I, Cuevas E, Lazaro I, Martin C, Cigudosa JC and Silva A: p53 regulates the self-renewal and differentiation of neural precursors. Neuroscience. 158:1378–1389. 2009. View Article : Google Scholar

53 

Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, Koh C, Zhang J, Li YM, Maciaczyk J, et al: NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells. 28:5–16. 2010.

54 

Xu R, Shimizu F, Hovinga K, Beal K, Karimi S, Droms L, Peck KK, Gutin P, Iorgulescu JB, Kaley T, et al: Molecular and clinical effects of Notch inhibition in glioma patients: A phase 0/I trial. Clin Cancer Res. 22:4786–4796. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Tanaka S, Nakada M, Yamada D, Nakano I, Todo T, Ino Y, Hoshii T, Tadokoro Y, Ohta K, Ali MA, et al: Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells. J Neurooncol. 121:239–250. 2015. View Article : Google Scholar

56 

Goldfarb DS, Corbett AH, Mason DA, Harreman MT and Adam SA: Importin alpha: A multipurpose nuclear-transport receptor. Trends Cell Biol. 14:505–514. 2004. View Article : Google Scholar : PubMed/NCBI

57 

Huenniger K, Krämer A, Soom M, Chang I, Köhler M, Depping R, Kehlenbach RH and Kaether C: Notch1 signaling is mediated by importins alpha 3, 4, and 7. Cell Mol Life Sci. 67:3187–3196. 2010. View Article : Google Scholar : PubMed/NCBI

58 

Chen G, Kong J, Tucker-Burden C, Anand M, Rong Y, Rahman F, Moreno CS, Van Meir EG, Hadjipanayis CG and Brat DJ: Human Brat ortholog TRIM3 is a tumor suppressor that regulates asymmetric cell division in glioblastoma. Cancer Res. 74:4536–4548. 2014. View Article : Google Scholar : PubMed/NCBI

59 

Mukherjee S, Tucker-Burden C, Zhang C, Moberg K, Read R, Hadjipanayis C and Brat DJ: Drosophila brat and human ortholog TRIM3 maintain stem cell equilibrium and suppress brain tumorigenesis by attenuating Notch nuclear transport. Cancer Res. 76:2443–2452. 2016. View Article : Google Scholar : PubMed/NCBI

60 

Gagliardi F, Narayanan A, Reni M, Franzin A, Mazza E, Boari N, Bailo M, Zordan P and Mortini P: The role of CXCR4 in highly malignant human gliomas biology: Current knowledge and future directions. Glia. 62:1015–1023. 2014. View Article : Google Scholar : PubMed/NCBI

61 

Calinescu AA, Yadav VN, Carballo E, Kadiyala P, Tran D, Zamler DB, Doherty R, Srikanth M, Lowenstein PR and Castro MG: Survival and proliferation of neural progenitor-derived glioblastomas under hypoxic stress is controlled by a CXCL12/CXCR4 autocrine-positive feedback mechanism. Clin Cancer Res. 23:1250–1262. 2017. View Article : Google Scholar

62 

Yi L, Zhou X, Li T, Liu P, Hai L, Tong L, Ma H, Tao Z, Xie Y, Zhang C, et al: Notch1 signaling pathway promotes invasion, self-renewal and growth of glioma initiating cells via modulating chemokine system CXCL12/CXCR4. J Exp Clin Cancer Res. 38:3392019. View Article : Google Scholar : PubMed/NCBI

63 

Iso T, Kedes L and Hamamori Y: HES and HERP families: Multiple effectors of the Notch signaling pathway. J Cell Physiol. 194:237–255. 2003. View Article : Google Scholar : PubMed/NCBI

64 

Tay J and Richter JD: Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice. Dev Cell. 1:201–213. 2001. View Article : Google Scholar : PubMed/NCBI

65 

Yin J, Park G, Lee JE, Park JY, Kim TH, Kim YJ, Lee SH, Yoo H, Kim JH and Park JB: CPEB1 modulates differentiation of glioma stem cells via downregulation of HES1 and SIRT1 expression. Oncotarget. 5:6756–6769. 2014. View Article : Google Scholar : PubMed/NCBI

66 

Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, Kedes L and Hamamori Y: HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling. Mol Cell Biol. 21:6080–6089. 2001. View Article : Google Scholar : PubMed/NCBI

67 

Iso T, Sartorelli V, Chung G, Shichinohe T, Kedes L and Hamamori Y: HERP, a new primary target of Notch regulated by ligand binding. Mol Cell Biol. 21:6071–6079. 2001. View Article : Google Scholar : PubMed/NCBI

68 

Sokol SY: Maintaining embryonic stem cell pluripotency with Wnt signaling. Development. 138:4341–4350. 2011. View Article : Google Scholar : PubMed/NCBI

69 

Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP, Andrew D, Nathans J and Nusse R: A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature. 382:225–230. 1996. View Article : Google Scholar : PubMed/NCBI

70 

Wehrli M, Dougan ST, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A and DiNardo S: arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature. 407:527–530. 2000. View Article : Google Scholar : PubMed/NCBI

71 

Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B and Clevers H: Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science. 275:1784–1787. 1997. View Article : Google Scholar : PubMed/NCBI

72 

Hamada F and Bienz M: The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell. 7:677–685. 2004. View Article : Google Scholar : PubMed/NCBI

73 

Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O and Clevers H: XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 86:391–399. 1996. View Article : Google Scholar : PubMed/NCBI

74 

Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R and Birchmeier W: Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 382:638–642. 1996. View Article : Google Scholar : PubMed/NCBI

75 

Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG and Kemler R: Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev. 59:3–10. 1996. View Article : Google Scholar : PubMed/NCBI

76 

Takahashi-Yanaga F and Kahn M: Targeting Wnt signaling: Can we safely eradicate cancer stem cells? Clin Cancer Res. 16:3153–3162. 2010. View Article : Google Scholar : PubMed/NCBI

77 

Rajakulendran N, Rowland KJ, Selvadurai HJ, Ahmadi M, Park NI, Naumenko S, Dolma S, Ward RJ, So M, Lee L, et al: Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells. Genes Dev. 33:498–510. 2019. View Article : Google Scholar : PubMed/NCBI

78 

Sonoda Y, Ozawa T, Aldape KD, Deen DF, Berger MS and Pieper RO: Akt pathway activation converts anaplastic astrocytoma to glioblastoma multiforme in a human astrocyte model of glioma. Cancer Res. 61:6674–6678. 2001.PubMed/NCBI

79 

Morgan RG, Ridsdale J, Payne M, Heesom KJ, Wilson MC, Davidson A, Greenhough A, Davies S, Williams AC, Blair A, et al: LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells. Haematologica. 104:1365–1377. 2019. View Article : Google Scholar : PubMed/NCBI

80 

Chen J, Liu G, Wu Y, Ma J, Wu H, Xie Z, Chen S, Yang Y, Wang S, Shen P, et al: CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to enhance the transcriptional activity of β-catenin/LEF1 complex via effects on chromatin remodeling. Mol Cancer. 18:1502019. View Article : Google Scholar

81 

Brown DM and Ruoslahti E: Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 5:365–374. 2004. View Article : Google Scholar : PubMed/NCBI

82 

Hu B, Emdad L, Bacolod MD, Kegelman TP, Shen XN, Alzubi MA, Das SK, Sarkar D and Fisher PB: Astrocyte elevated gene-1 interacts with Akt isoform 2 to control glioma growth, survival, and pathogenesis. Cancer Res. 74:7321–7332. 2014. View Article : Google Scholar : PubMed/NCBI

83 

Hu B, Emdad L, Kegelman TP, Shen XN, Das SK, Sarkar D and Fisher PB: Astrocyte elevated Gene-1 regulates β-catenin signaling to maintain glioma stem-like stemness and self-renewal. Mol Cancer Res. 15:225–233. 2017. View Article : Google Scholar

84 

Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK and Moestrup SK: Identification of the haemoglobin scavenger receptor. Nature. 409:198–201. 2001. View Article : Google Scholar : PubMed/NCBI

85 

Ostuni R, Kratochvill F, Murray PJ and Natoli G: Macrophages and cancer: From mechanisms to therapeutic implications. Trends Immunol. 36:229–239. 2015. View Article : Google Scholar : PubMed/NCBI

86 

Shi Y, Ping YF, Zhou W, He ZC, Chen C, Bian BS, Zhang L, Chen L, Lan X, Zhang XC, et al: Tumour-associated macro-phages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth. Nat Commun. 8:150802017. View Article : Google Scholar

87 

Ritter M, Buechler C, Kapinsky M and Schmitz G: Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. Eur J Immunol. 31:999–1009. 2001. View Article : Google Scholar : PubMed/NCBI

88 

Di Maira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, Pinna LA and Ruzzene M: Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell Death Differ. 12:668–677. 2005. View Article : Google Scholar : PubMed/NCBI

89 

Chen T, Chen J, Zhu Y, Li Y, Wang Y, Chen H, Wang J, Li X, Liu Y, Li B, et al: CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2. Oncogene. 38:1183–1199. 2019. View Article : Google Scholar

90 

Wang F, Wang AY, Chesnelong C, Yang Y, Nabbi A, Thalappilly S, Alekseev V and Riabowol K: ING5 activity in self-renewal of glioblastoma stem cells via calcium and follicle stimulating hormone pathways. Oncogene. 37:286–301. 2018. View Article : Google Scholar :

91 

Zhu Q, Shen Y, Chen X, He J, Liu J and Zu X: Self-renewal signalling pathway inhibitors: Perspectives on therapeutic approaches for cancer stem cells. OncoTargets Ther. 13:525–540. 2020. View Article : Google Scholar

92 

Handschumacher RE, Harding MW, Rice J, Drugge RJ and Speicher DW: Cyclophilin: A specific cytosolic binding protein for cyclosporin A. Science. 226:544–547. 1984. View Article : Google Scholar : PubMed/NCBI

93 

Sun S, Wang Q, Giang A, Cheng C, Soo C, Wang C, Liu L and Chiu R: Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB. J Neurooncol. 101:1–14. 2011. View Article : Google Scholar

94 

Wang G, Shen J, Sun J, Jiang Z, Fan J, Wang H, Yu S, Long Y, Liu Y, Bao H, et al: Cyclophilin A maintains glioma-initiating cell stemness by regulating Wnt/β-catenin signaling. Clin Cancer Res. 23:6640–6649. 2017. View Article : Google Scholar : PubMed/NCBI

95 

Machold R, Hayashi S, Rutlin M, Muzumdar MD, Nery S, Corbin JG, Gritli-Linde A, Dellovade T, Porter JA, Rubin LL, et al: Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron. 39:937–950. 2003. View Article : Google Scholar : PubMed/NCBI

96 

Micchelli CA, The I, Selva E, Mogila V and Perrimon N: Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling. Development. 129:843–851. 2002. View Article : Google Scholar : PubMed/NCBI

97 

Takebe N, Harris PJ, Warren RQ and Ivy SP: Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol. 8:97–106. 2011. View Article : Google Scholar

98 

Ruiz i Altaba A and Altaba A: Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development. 125:2203–2212. 1998. View Article : Google Scholar : PubMed/NCBI

99 

Baylin SB and Jones PA: Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol. 8:a0195052016. View Article : Google Scholar : PubMed/NCBI

100 

Marampon F, Megiorni F, Camero S, Crescioli C, McDowell HP, Sferra R, Vetuschi A, Pompili S, Ventura L, De Felice F, et al: HDAC4 and HDAC6 sustain DNA double strand break repair and stem-like phenotype by promoting radioresistance in glioblastoma cells. Cancer Lett. 397:1–11. 2017. View Article : Google Scholar : PubMed/NCBI

101 

Yang W, Liu Y, Gao R, Yu H and Sun T: HDAC6 inhibition induces glioma stem cells differentiation and enhances cellular radiation sensitivity through the SHH/Gli1 signaling pathway. Cancer Lett. 415:164–176. 2018. View Article : Google Scholar

102 

Auzmendi-Iriarte J, Saenz-Antoñanzas A, Mikelez-Alonso I, Carrasco-Garcia E, Tellaetxe-Abete M, Lawrie CH, Sampron N, Cortajarena AL and Matheu A: Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma. Cell Death Dis. 11:4172020. View Article : Google Scholar : PubMed/NCBI

103 

Dolatabadi S, Jonasson E, Lindén M, Fereydouni B, Bäcksten K, Nilsson M, Martner A, Forootan A, Fagman H, Landberg G, et al: JAK-STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma. Int J Cancer. 145:435–449. 2019. View Article : Google Scholar : PubMed/NCBI

104 

Zhang C, Mukherjee S, Tucker-Burden C, Ross JL, Chau MJ, Kong J and Brat DJ: TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3. Mol Oncol. 11:280–294. 2017. View Article : Google Scholar : PubMed/NCBI

105 

Shi Y, Zhou W, Cheng L, Chen C, Huang Z, Fang X, Wu Q, He Z, Xu S, Lathia JD, et al: Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells. Cell Death Differ. 24:167–180. 2017. View Article : Google Scholar :

106 

Lasorella A, Benezra R and Iavarone A: The ID proteins: Master regulators of cancer stem cells and tumour aggressiveness. Nat Rev Cancer. 14:77–91. 2014. View Article : Google Scholar : PubMed/NCBI

107 

Lee JK, Chang N, Yoon Y, Yang H, Cho H, Kim E, Shin Y, Kang W, Oh YT, Mun GI, et al: USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance. Neuro Oncol. 18:37–47. 2016. View Article : Google Scholar

108 

Cook PJ, Thomas R, Kingsley PJ, Shimizu F, Montrose DC, Marnett LJ, Tabar VS, Dannenberg AJ and Benezra R: Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma. Neuro Oncol. 18:1379–1389. 2016. View Article : Google Scholar : PubMed/NCBI

109 

Jin X, Jeon HM, Jin X, Kim EJ, Yin J, Jeon HY, Sohn YW, Oh SY, Kim JK, Kim SH, et al: The ID1-CULLIN3 axis regulates intracellular SHH and WNT signaling in glioblastoma stem cells. Cell Rep. 16:1629–1641. 2016. View Article : Google Scholar : PubMed/NCBI

110 

Jin X, Jin X, Kim LJY, Dixit D, Jeon HY, Kim EJ, Kim JK, Lee SY, Yin J, Rich JN, et al: Inhibition of ID1-BMPR2 Intrinsic Signaling Sensitizes Glioma Stem Cells to Differentiation Therapy. Clin Cancer Res. 24:383–394. 2018. View Article : Google Scholar

111 

Sareddy GR, Viswanadhapalli S, Surapaneni P, Suzuki T, Brenner A and Vadlamudi RK: Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway. Oncogene. 36:2423–2434. 2017. View Article : Google Scholar :

112 

Dali R, Verginelli F, Pramatarova A, Sladek R and Stifani S: Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells. Mol Oncol. 12:775–787. 2018. View Article : Google Scholar : PubMed/NCBI

113 

Semenza GL: Dynamic regulation of stem cell specification and maintenance by hypoxia-inducible factors. Mol Aspects Med. 47-48:15–23. 2016. View Article : Google Scholar

114 

Ong DST, Hu B, Ho YW, Sauvé CG, Bristow CA, Wang Q, Multani AS, Chen P, Nezi L, Jiang S, et al: PAF promotes stemness and radioresistance of glioma stem cells. Proc Natl Acad Sci USA. 114:E9086–E9095. 2017. View Article : Google Scholar : PubMed/NCBI

115 

Kwon SJ, Kwon OS, Kim KT, Go YH, Yu SI, Lee BH, Miyoshi H, Oh E, Cho SJ and Cha HJ: Role of MEK partner-1 in cancer stemness through MEK/ERK pathway in cancerous neural stem cells, expressing EGFRviii. Mol Cancer. 16:1402017. View Article : Google Scholar : PubMed/NCBI

116 

Gravina GL, Mancini A, Colapietro A, Delle Monache S, Sferra R, Vitale F, Cristiano L, Martellucci S, Marampon F, Mattei V, et al: The small molecule Ephrin receptor inhibitor, glpg1790, reduces renewal capabilities of cancer stem cells, showing anti-tumour efficacy on preclinical glioblastoma models. Cancers (Basel). 11:3592019. View Article : Google Scholar

117 

Bandey I, Chiou SH, Huang AP, Tsai JC and Tu PH: Progranulin promotes Temozolomide resistance of glioblastoma by orchestrating DNA repair and tumor stemness. Oncogene. 34:1853–1864. 2015. View Article : Google Scholar

118 

Xu Q, Hu C, Zhu Y, Wang K, Lal B, Li L, Tang J, Wei S, Huang G, Xia S, et al: ShRNA-based POLD2 expression knockdown sensitizes glioblastoma to DNA-Damaging therapeutics. Cancer Lett. 482:126–135. 2020. View Article : Google Scholar : PubMed/NCBI

119 

Hitomi M, Deleyrolle LP, Mulkearns-Hubert EE, Jarrar A, Li M, Sinyuk M, Otvos B, Brunet S, Flavahan WA, Hubert CG, et al: Differential connexin function enhances self-renewal in glioblastoma. Cell Rep. 11:1031–1042. 2015. View Article : Google Scholar : PubMed/NCBI

120 

Arrizabalaga O, Moreno-Cugnon L, Auzmendi-Iriarte J, Aldaz P, Ibanez de Caceres I, Garros-Regulez L, Moncho-Amor V, Torres-Bayona S, Pernía O, Pintado-Berninches L, et al: High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response. Oncogenesis. 6:4012017. View Article : Google Scholar : PubMed/NCBI

121 

Degrauwe N, Schlumpf TB, Janiszewska M, Martin P, Cauderay A, Provero P, Riggi N, Suvà ML, Paro R and Stamenkovic I: The RNA binding protein IMP2 preserves glioblastoma stem cells by preventing let-7 target gene silencing. Cell Rep. 15:1634–1647. 2016. View Article : Google Scholar : PubMed/NCBI

122 

Iwamaru A, Szymanski S, Iwado E, Aoki H, Yokoyama T, Fokt I, Hess K, Conrad C, Madden T, Sawaya R, et al: A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. Oncogene. 26:2435–2444. 2007. View Article : Google Scholar

123 

Ott M, Kassab C, Marisetty A, Hashimoto Y, Wei J, Zamler D, Leu JS, Tomaszowski KH, Sabbagh A, Fang D, et al: Radiation with STAT3 blockade triggers dendritic cell-T cell interactions in the glioma microenvironment and therapeutic efficacy. Clin Cancer Res. 26:4983–4994. 2020. View Article : Google Scholar : PubMed/NCBI

124 

Lim D, Kim KS, Kim H, Ko KC, Song JJ, Choi JH, Shin M, Min JJ, Jeong JH and Choy HE: Anti-tumor activity of an immunotoxin (TGFα-PE38) delivered by attenuated Salmonella typhimurium. Oncotarget. 8:37550–37560. 2017. View Article : Google Scholar : PubMed/NCBI

125 

Sampson JH, Akabani G, Archer GE, Berger MS, Coleman RE, Friedman AH, Friedman HS, Greer K, Herndon JE II, Kunwar S, et al: Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors. Neuro Oncol. 10:320–329. 2008. View Article : Google Scholar : PubMed/NCBI

126 

Hau P, Jachimczak P, Schlingensiepen R, Schulmeyer F, Jauch T, Steinbrecher A, Brawanski A, Proescholdt M, Schlaier J, Buchroithner J, et al: Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides. 17:201–12. 2007. View Article : Google Scholar : PubMed/NCBI

127 

Rodon J, Carducci MA, Sepulveda-Sánchez JM, Azaro A, Calvo E, Seoane J, Braña I, Sicart E, Gueorguieva I, Cleverly AL, et al: First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. Clin Cancer Res. 21:553–560. 2015. View Article : Google Scholar

128 

Zhang M, Lahn M and Huber PE: Translating the combination of TGFβ blockade and radiotherapy into clinical development in glioblastoma. OncoImmunology. 1:943–945. 2012. View Article : Google Scholar : PubMed/NCBI

129 

Zhang M, Kleber S, Röhrich M, Timke C, Han N, Tuettenberg J, Martin-Villalba A, Debus J, Peschke P, Wirkner U, et al: Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res. 71:7155–7167. 2011. View Article : Google Scholar : PubMed/NCBI

130 

Pan E, Supko JG, Kaley TJ, Butowski NA, Cloughesy T, Jung J, Desideri S, Grossman S, Ye X and Park DM: Phase I study of RO4929097 with bevacizumab in patients with recurrent malignant glioma. J Neurooncol. 130:571–579. 2016. View Article : Google Scholar : PubMed/NCBI

131 

Yahyanejad S, King H, Iglesias VS, Granton PV, Barbeau LM, van Hoof SJ, Groot AJ, Habets R, Prickaerts J, Chalmers AJ, et al: NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma. Oncotarget. 7:41251–41264. 2016. View Article : Google Scholar : PubMed/NCBI

132 

Tolcher AW, Messersmith WA, Mikulski SM, Papadopoulos KP, Kwak EL, Gibbon DG, Patnaik A, Falchook GS, Dasari A, Shapiro GI, et al: Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol. 30:2348–2353. 2012. View Article : Google Scholar : PubMed/NCBI

133 

den Hollander MW, Bensch F, Glaudemans AW, Oude Munnink TH, Enting RH, den Dunnen WF, Heesters MA, Kruyt FA, Lub-de Hooge MN, Cees de Groot J, et al: TGF-β Antibody Uptake in Recurrent High-Grade Glioma Imaged with 89Zr-Fresolimumab PET. J Nucl Med. 56:1310–1314. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jin J, Grigore F, Chen CC and Li M: Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review). Int J Oncol 59: 45, 2021.
APA
Jin, J., Grigore, F., Chen, C.C., & Li, M. (2021). Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review). International Journal of Oncology, 59, 45. https://doi.org/10.3892/ijo.2021.5225
MLA
Jin, J., Grigore, F., Chen, C. C., Li, M."Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review)". International Journal of Oncology 59.1 (2021): 45.
Chicago
Jin, J., Grigore, F., Chen, C. C., Li, M."Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review)". International Journal of Oncology 59, no. 1 (2021): 45. https://doi.org/10.3892/ijo.2021.5225
Copy and paste a formatted citation
x
Spandidos Publications style
Jin J, Grigore F, Chen CC and Li M: Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review). Int J Oncol 59: 45, 2021.
APA
Jin, J., Grigore, F., Chen, C.C., & Li, M. (2021). Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review). International Journal of Oncology, 59, 45. https://doi.org/10.3892/ijo.2021.5225
MLA
Jin, J., Grigore, F., Chen, C. C., Li, M."Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review)". International Journal of Oncology 59.1 (2021): 45.
Chicago
Jin, J., Grigore, F., Chen, C. C., Li, M."Self‑renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review)". International Journal of Oncology 59, no. 1 (2021): 45. https://doi.org/10.3892/ijo.2021.5225
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team