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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
July-2021 Volume 22 Issue 1

Full Size Image

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 22 Issue 1

Full Size Image

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 Open Access

Autophagy-related signaling pathways are involved in cancer (Review)

  • Authors:
    • Caixia Chen
    • Hui Gao
    • Xiulan Su
  • View Affiliations / Copyright

    Affiliations: Clinical Medicine Research Center, The Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China, Department of Thoracic Surgery, Inner Mongolia Autonomous Region Cancer Hospital, Hohhot, Inner Mongolia 010020, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 710
    |
    Published online on: May 3, 2021
       https://doi.org/10.3892/etm.2021.10142
  • 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

Autophagy is a self-digestion process in cells that can maintain energy homeostasis under normal circumstances. However, misfolded proteins, damaged mitochondria and other unwanted components in cells can be decomposed and reused via autophagy in some specific cases (including hypoxic stress, low energy states or nutrient deprivation). Therefore, autophagy serves a positive role in cell survival and growth. However, excessive autophagy may lead to apoptosis. Furthermore, abnormal autophagy may lead to carcinogenesis and promote tumorigenesis in normal cells. In tumor cells, autophagy may provide the energy required for excessive proliferation, promote the growth of cancer cells, and evade apoptosis caused by certain treatments, including radiotherapy and chemotherapy, resulting in increased treatment resistance and drug resistance. On the other hand, autophagy leads to an insufficient nutrient supply in cancer cells and the destruction of energy homeostasis, thereby inducing cancer cell apoptosis. Therefore, understanding the mechanism of the double-edged sword of autophagy is crucial for the treatment of cancer. The present review summarizes the signaling pathways and key factors involved in autophagy and cancer to provide possible strategies for treating tumors.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Klionsky DJ: Autophagy revisited: A conversation with Christian de Duve. Autophagy. 4:740–743. 2008.PubMed/NCBI View Article : Google Scholar

2 

Nakatogawa H, Suzuki K, Kamada Y and Ohsumi Y: Dynamics and diversity in autophagy mechanisms: Lessons from yeast. Nat Rev Mol Cell Biol. 10:458–467. 2009.PubMed/NCBI View Article : Google Scholar

3 

Yamamoto H, Fujioka Y, Suzuki SW, Noshiro D, Suzuki H, Kondo-Kakuta C, Kimura Y, Hirano H, Ando T, Noda NN, et al: The intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy initiation complexes. Dev Cell. 38:86–99. 2016.PubMed/NCBI View Article : Google Scholar

4 

Byun S, Lee E and Lee KW: Therapeutic implications of autophagy inducers in immunological disorders, infection, and cancer. Int J Mol Sci. 18:1959–1980. 2017.PubMed/NCBI View Article : Google Scholar

5 

Ma X, Yin X, Liu H, Chen Q, Feng Y, Ma X and Liu W: Antiproliferative activity of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) in human gastric carcinoma cells is facilitated via activation of autophagic pathway, mitochondrial-mediated programmed cell death and inhibition of cell migration and invasion. J BUON. 24:2000–2005. 2019.PubMed/NCBI

6 

Khan M, Imam H and Siddiqui A: Subversion of cellular autophagy during virus infection: Insights from hepatitis B and hepatitis C viruses. Liver Res. 2:146–156. 2018.PubMed/NCBI View Article : Google Scholar

7 

Yan X, Zhou R and Ma Z: Autophagy-cell survival and death. Adv Exp Med Biol. 1206:667–696. 2019.PubMed/NCBI View Article : Google Scholar

8 

Shen MX and Ding JB: Expression levels and roles of EMC-6, Beclin1, and Rab5a in the cervical cancer. Eur Rev Med Pharmacol Sci. 21:3038–3046. 2017.PubMed/NCBI

9 

Yu S, Cheng C, Wang J, Wang J, Qu Z, Ren H, Li Y, Ning Q, Chen M and Hu T: Loss of Beclin1 expression and Nrf2 overexpression are associated with poor survival of patients with non-small cell lung cancer. Anticancer Agents Med Chem. 18:1680–1687. 2018.PubMed/NCBI View Article : Google Scholar

10 

Wu S, Sun C, Tian D, Li Y, Gao X, He S and Li T: Expression and clinical significances of Beclin1, LC3 and mTOR in colorectal cancer. Int J Clin Exp Pathol. 8:3882–3891. 2015.PubMed/NCBI

11 

Chen JH, Zhang P, Chen WD, Li DD, Wu XQ, Deng R, Jiao L, Li X, Ji J, Feng GK, et al: ATM-mediated PTEN phosphorylation promotes PTEN nuclear translocation and autophagy in response to DNA-damaging agents in cancer cells. Autophagy. 11:239–252. 2015.PubMed/NCBI View Article : Google Scholar

12 

Wang Z, Wang N, Liu P and Xie X: AMPK and Cancer. Exp Suppl. 107:203–226. 2016.PubMed/NCBI View Article : Google Scholar

13 

Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA and Cantley LC: The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell. 6:91–99. 2004.PubMed/NCBI View Article : Google Scholar

14 

Li H, Cao X, Chen X, Yi X, Xia J, Chen J and Yang L: Bufadienolides induce apoptosis and autophagy by inhibiting the AKT signaling pathway in melanoma A-375 cells. Mol Med Rep. 20:2347–2354. 2019.PubMed/NCBI View Article : Google Scholar

15 

Zhang J, Zhao D, Xie Z and Qi Y: Down-regulation of AKT combined with radiation-induced autophagy and apoptosis roles in MCF-7 cells. Biomed Mater Eng. 26 (Suppl 1):S2259–S2265. 2015.PubMed/NCBI View Article : Google Scholar

16 

Jiao YN, Wu LN, Xue D, Liu XJ, Tian ZH, Jiang ST, Han SY and Li PP: Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells. Cancer Cell Int. 18(149)2018.PubMed/NCBI View Article : Google Scholar

17 

Zhou J, Chong SY, Lim A, Singh BK, Sinha RA, Salmon AB and Yen PM: Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging (Albany NY). 9:583–599. 2017.PubMed/NCBI View Article : Google Scholar

18 

Oczypok EA, Oury TD and Chu CT: It's a cell-eat-cell world: Autophagy and phagocytosis. Am J Pathol. 182:612–622. 2013.PubMed/NCBI View Article : Google Scholar

19 

Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M and Kim DH: ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 20:1992–2003. 2009.PubMed/NCBI View Article : Google Scholar

20 

Zhan ZZ, Chen X and Zhang Y: Autophagy and the relativity of its function. Di Er Jun Yi Da Xue Xue Bao. 37:1189–1194. 2016.PubMed/NCBI View Article : Google Scholar

21 

Kim SH, Yu HS, Park S, Park HG, Ahn YM, Kang UG and Kim YS: Electroconvulsive seizures induce autophagy by activating the AMPK signaling pathway in the rat frontal cortex. Int J Neuropsychopharmacol. 23:45–52. 2020.PubMed/NCBI View Article : Google Scholar

22 

Chang H, Peng X, Yan X, Zhang J, Xu S, Wang H, Wang Z, Ma X and Gao Y: Autophagy and Akt-mTOR signaling display periodic oscillations during torpor-arousal cycles in oxidative skeletal muscle of Daurian ground squirrels (Spermophilus dauricus). J Comp Physiol B 15: 2019. https://doi.org/10.1007/s00360-019-01245-5.

23 

Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y and Yoshimori T: LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 117:2805–2812. 2004.PubMed/NCBI View Article : Google Scholar

24 

Wang Y, Li L, Hou C, Lai Y, Long J, Liu J, Zhong Q and Diao J: SNARE-mediated membrane fusion in autophagy. Semin Cell Dev Biol. 60:97–104. 2016.PubMed/NCBI View Article : Google Scholar

25 

Cheng X, Ma X, Zhu Q, Song D, Ding X, Li L, Jiang X, Wang X, Tian R, Su H, et al: Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of autophagosome maturation and lipid metabolism. Mol Cell. 73:788–802.e7. 2019.PubMed/NCBI View Article : Google Scholar

26 

Eskelinen EL: Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med. 27:495–502. 2006.PubMed/NCBI View Article : Google Scholar

27 

Zhang H: Targeting autophagy in lymphomas: A double-edged sword? Int J Hematol. 107:502–512. 2018.PubMed/NCBI View Article : Google Scholar

28 

Nagar R: Autophagy: A brief overview in perspective of dermatology. Indian J Dermatol Venereol Leprol. 83:290–297. 2017.PubMed/NCBI View Article : Google Scholar

29 

Rustin M: Postmodernism and antimodernism in contemporary British architecture. Assemblage. 10:89–103. 1989.

30 

Nakamura O, Hitora T, Yamagami Y, Mori M, Nishimura H, Horie R, et al: The combination of rapamycin and MAPK inhibitors enhances the growth inhibitory effect on Nara-H cells. Int J Mol Med. 33:1491–1497. 2014.PubMed/NCBI View Article : Google Scholar

31 

Reddy D, Kumavath R, Tan TZ, Ampasala DR and Kumar AP: Peruvoside targets apoptosis and autophagy through MAPK Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways in human cancers. Life Sci. 241(117147)2020.PubMed/NCBI View Article : Google Scholar

32 

Bhaskar PT and Hay N: The two TORCs and Akt. Dev Cell. 12:487–502. 2007.PubMed/NCBI View Article : Google Scholar

33 

Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P and Hall MN: Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. 10:457–468. 2002.PubMed/NCBI View Article : Google Scholar

34 

Julien LA, Carriere A, Moreau J and Roux PP: mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol. 30:908–921. 2010.PubMed/NCBI View Article : Google Scholar

35 

Wang Y and Zhang H: Regulation of autophagy by mTOR signaling pathway. Adv Exp Med Biol. 1206:67–83. 2019.PubMed/NCBI View Article : Google Scholar

36 

Petherick KJ, Conway OJ, Mpamhanga C, Osborne SA, Kamal A, Saxty B and Ganley IG: Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem. 290:11376–11383. 2015.PubMed/NCBI View Article : Google Scholar

37 

Joseph B, Kumar RV, Champaka G, Shenoy A, Sabitha KS, Lokesh V, Ramesh C and Vijay CR: Biological tailoring of adjuvant radiotherapy in head and neck and oral malignancies - The potential role of p53 and eIF4E as predictive parameters. Indian J Cancer. 56:330–334. 2019.PubMed/NCBI View Article : Google Scholar

38 

Huang CI, Wang CC, Tai TS, Hwang TZ, Yang CC, Hsu CM and Su YC: eIF4E and 4EBP1 are prognostic markers of head and neck squamous cell carcinoma recurrence after definitive surgery and adjuvant radiotherapy. PLoS One. 14(e0225537)2019.PubMed/NCBI View Article : Google Scholar

39 

Alabdullah ML, Ahmad DA, Moseley P, Madhusudan S, Chan S and Rakha E: The mTOR downstream regulator (p-4EBP1) is a novel independent prognostic marker in ovarian cancer. J Obstet Gynaecol. 39:522–528. 2019.PubMed/NCBI View Article : Google Scholar

40 

Gleason CE, Oses-Prieto JA, Li KH, Saha B, Situ G, Burlingame AL and Pearce D: Phosphorylation at distinct subcellular locations underlies specificity in mTORC2-mediated activation of SGK1 and Akt. J Cell Sci. 132:1–16. 2019.PubMed/NCBI View Article : Google Scholar

41 

Liu Y, Ao X, Ding W, Ponnusamy M, Wu W, Hao X, Yu W, Wang Y, Li P and Wang J: Critical role of FOXO3a in carcinogenesis. Mol Cancer. 17:104–115. 2018.PubMed/NCBI View Article : Google Scholar

42 

Ni HM, Du K, You M and Ding WX: Critical role of FoxO3a in alcohol-induced autophagy and hepatotoxicity. Am J Pathol. 183:1815–1825. 2013.PubMed/NCBI View Article : Google Scholar

43 

Carnero A and Paramio JM: The PTEN/PI3K/AKT pathway in vivo, cancer mouse models. Front Oncol. 4(252)2014.PubMed/NCBI View Article : Google Scholar

44 

Carnero A, Blanco-Aparicio C, Renner O, Link W and Leal JF: The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets. 8:187–198. 2008.PubMed/NCBI View Article : Google Scholar

45 

Mangé A, Coyaud E, Desmetz C, Laurent E, Béganton B, Coopman P, Raught B and Solassol J: FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer. Theranostics. 9:7003–7015. 2019.PubMed/NCBI View Article : Google Scholar

46 

Wang P, Gao W, Wang Y and Wang J: Acetylshikonin inhibits in vitro and in vivo tumorigenesis in cisplatin-resistant oral cancer cells by inducing autophagy, programmed cell death and targeting m-TOR/PI3K/Akt signalling pathway. J BUON. 24:2062–2067. 2019.PubMed/NCBI

47 

Huang S, Xie T and Liu W: Icariin inhibits the growth of human cervical cancer cells by inducing apoptosis and autophagy by targeting mTOR/PI3K/AKT signalling pathway. J BUON. 24:990–996. 2019.PubMed/NCBI

48 

Agostini D, Natalucci V, Baldelli G, De Santi M, Donati Zeppa S, Vallorani L, Annibalini G, Lucertini F, Federici A, Izzo R, Stocchi V and Barbieri E: New insights into the role of exercise in inhibiting mTOR signaling in triple-negative breast cancer. Oxid Med Cell Longev. 2018(5896786)2018.PubMed/NCBI View Article : Google Scholar : https://doi.org/10.1155/2018/5896786.

49 

Han Y, Shi D and Li J: Inhibition of nasopharyngeal carcinoma by beta-lapachone occurs by targeting the mammalian target of rapamycin (mTOR)/PI3K/AKT pathway, reactive oxygen species (ROS) production, and autophagy induction. Med Sci Monit. 25:8995–9002. 2019.PubMed/NCBI View Article : Google Scholar

50 

Liu J, Ren Y, Hou Y, Zhang C, Wang B, Li X, Sun R and Liu J: Dihydroartemisinin induces endothelial cell autophagy through suppression of the Akt/mTOR pathway. J Cancer. 10:6057–6064. 2019.PubMed/NCBI View Article : Google Scholar

51 

Dong F, Han J, Jing G, Chen X, Yan S, Yue L, Cao Z, Liu X, Ma G and Liu J: Dihydroartemisinin transiently activates the JNK/SAPK signaling pathway in endothelial cells. Oncol Lett. 12:4699–4704. 2016.PubMed/NCBI View Article : Google Scholar

52 

Li WD, Zhou DM, Sun LL, Xiao L, Liu Z, Zhou M, Wang WB and Li XQ: LncRNA WTAPP1 promotes migration and angiogenesis of endothelial progenitor cells via MMP1 through microRNA 3120 and Akt/PI3K/autophagy pathways. Stem Cells. 36:1863–1874. 2018.PubMed/NCBI View Article : Google Scholar

53 

Liu R, Chen Z, Yi X, Huang F, Hu G, Liu D, Li X, Zhou H and Liu Z: 9za plays cytotoxic and proapoptotic roles and induces cytoprotective autophagy through the PDK1/Akt/mTOR axis in non-small-cell lung cancer. J Cell Physiol. 234:20728–20741. 2019.PubMed/NCBI View Article : Google Scholar

54 

Dowling RJ, Topisirovic I, Fonseca BD and Sonenberg N: Dissecting the role of mTOR: Lessons from mTOR inhibitors. Biochim Biophys Acta. 1804:433–439. 2010.PubMed/NCBI View Article : Google Scholar

55 

Gera J and Lichtenstein A: The mammalian target of rapamycin pathway as a therapeutic target in multiple myeloma. Leuk Lymphoma. 52:1857–1866. 2011.PubMed/NCBI View Article : Google Scholar

56 

Engelman JA, Luo J and Cantley LC: The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 7:606–619. 2006.PubMed/NCBI View Article : Google Scholar

57 

Tan FH, Bai Y, Saintigny P and Darido C: mTOR signalling in head and neck cancer: Heads Up. Cells. 8(333)2019.PubMed/NCBI View Article : Google Scholar

58 

Bu Z and Ji J: Therapeutic implications of mTOR inhibitors in the treatment of gastric cancer. Curr Cancer Drug Targets. 13:121–125. 2013.PubMed/NCBI View Article : Google Scholar

59 

Alvarez RH, Bechara RI, Naughton MJ, Adachi JA and Reuben JM: Emerging perspectives on mTOR inhibitor-associated pneumonitis in breast cancer. Oncologist. 23:660–669. 2018.PubMed/NCBI View Article : Google Scholar

60 

Chang L, Graham PH, Ni J, Hao J, Bucci J, Cozzi PJ and Li Y: Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance. Crit Rev Oncol Hematol. 96:507–517. 2015.PubMed/NCBI View Article : Google Scholar

61 

Myers AP: New strategies in endometrial cancer: Targeting the PI3K/mTOR pathway--the devil is in the details. Clin Cancer Res. 19:5264–5274. 2013.PubMed/NCBI View Article : Google Scholar

62 

Wu CE, Chen MH and Yeh CN: mTOR inhibitors in advanced biliary tract cancers. Int J Mol Sci. 20(500)2019.PubMed/NCBI View Article : Google Scholar : https://doi.org/10.3390/ijms20030500.

63 

Ching CB and Hansel DE: Expanding therapeutic targets in bladder cancer: The PI3K/Akt/mTOR pathway. Lab Invest. 90:1406–1414. 2010.PubMed/NCBI View Article : Google Scholar

64 

Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de Stanchina E, et al: Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 534:272–276. 2016.PubMed/NCBI View Article : Google Scholar

65 

Yu C, Sun P, Zhou Y, Shen B, Zhou M, Wu L and Kong M: Inhibition of AKT enhances the anti-cancer effects of Artemisinin in clear cell renal cell carcinoma. Biomed Pharmacother. 118(109383)2019.PubMed/NCBI View Article : Google Scholar

66 

Vinayak S and Carlson RW: mTOR inhibitors in the treatment of breast cancer. Oncology (Williston Park). 27:38–44, 46, 48 passim. 2013.PubMed/NCBI

67 

Martisova A, Sommerova L, Kuricova K, Podhorec J, Vojtesek B, Kankova K and Hrstka R: AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy. Oncol Lett. 18:4964–4973. 2019.PubMed/NCBI View Article : Google Scholar

68 

Ciccarese F, Zulato E and Indraccolo S: LKB1/AMPK pathway and drug response in cancer: A therapeutic perspective. Oxid Med Cell Longev. 2019(8730816)2019.PubMed/NCBI View Article : Google Scholar

69 

Richani D, Lavea CF, Kanakkaparambil R, Riepsamen AH, Bertoldo MJ, Bustamante S and Gilchrist RB: Participation of the adenosine salvage pathway and cyclic AMP modulation in oocyte energy metabolism. Sci Rep. 9:18395–18406. 2019.PubMed/NCBI View Article : Google Scholar

70 

Lu C, Wang W, Jia Y, Liu X, Tong Z and Li B: Inhibition of AMPK/autophagy potentiates parthenolide-induced apoptosis in human breast cancer cells. J Cell Biochem. 115:1458–1466. 2014.PubMed/NCBI View Article : Google Scholar

71 

Chen W, Pan Y, Wang S, Liu Y, Chen G, Zhou L, Zhang C, Ni W, Wang A, Lu Y, et al: Correction to: cryptotanshinone activates AMPK-TSC2 axis leading to inhibition of mTORC1 signaling in cancer cells. BMC Cancer. 19:257–269. 2019.PubMed/NCBI View Article : Google Scholar

72 

Andrade BM and de Carvalho DP: Perspectives of the AMP-activated kinase (AMPK) signalling pathway in thyroid cancer. Biosci Rep. 34(e00105)2014.PubMed/NCBI View Article : Google Scholar

73 

Li F, Yang C, Zhang HB, Ma J, Jia J, Tang X, Zeng J, Chong T, Wang X, He D, et al: BET inhibitor JQ1 suppresses cell proliferation via inducing autophagy and activating LKB1/AMPK in bladder cancer cells. Cancer Med. 8:4792–4805. 2019.PubMed/NCBI View Article : Google Scholar

74 

Zhao Z, Feng L, Wang J, Cheng D, Liu M, Ling M, Xu W and Sun K: NPC-26 kills human colorectal cancer cells via activating AMPK signaling. Oncotarget. 8:18312–18321. 2017.PubMed/NCBI View Article : Google Scholar

75 

Chen L, Liu M, Luan Y and Liu Y, Zhang Z, Ma B, Liu X and Liu Y: BMP-6 protects retinal pigment epithelial cells from oxidative stress-induced injury by inhibiting the MAPK signaling pathways. Int J Mol Med. 42:1096–1105. 2018.PubMed/NCBI View Article : Google Scholar

76 

Ma Z, Wang C, Liu C, Yan DY, Tan X, Liu K, Jing MJ, Deng Y, Liu W and Xu B: Manganese induces autophagy dysregulation: The role of S-nitrosylation in regulating autophagy related proteins in vivo and in vitro. Sci Total Environ. 698(134294)2020.PubMed/NCBI View Article : Google Scholar

77 

Pan MY, Shen YC, Lu CH, Yang SY, Ho TF, Peng YT and Chang CC: Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines. Toxicol Appl Pharmacol. 265:325–334. 2012.PubMed/NCBI View Article : Google Scholar

78 

Kim JS, Bae GE, Kim KH, Lee SI, Chung C, Lee D, Lee TH, Kwon IS and Yeo MK: Prognostic significance of LC3B and p62/SQSTM1 expression in gastric adenocarcinoma. Anticancer Res. 39:6711–6722. 2019.PubMed/NCBI View Article : Google Scholar

79 

Zhang J, Yang S, Xu B, Wang T, Zheng Y, Liu F, Ren F, Jiang J, Shi H, Zou B, et al: p62 functions as an oncogene in colorectal cancer through inhibiting apoptosis and promoting cell proliferation by interacting with the vitamin D receptor. Cell Prolif. 52(e12585)2019.PubMed/NCBI View Article : Google Scholar

80 

Tan P, Ye Y, He L, Xie J, Jing J, Ma G, Pan H, Han L, Han W and Zhou Y: TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10. PLoS Biol. 16(e3000051)2018.PubMed/NCBI View Article : Google Scholar

81 

Schläfli AM, Adams O, Galván JA, Gugger M, Savic S, Bubendorf L, Schmid RA, Becker KF, Tschan MP, Langer R, et al: Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer. Oncotarget. 7:39544–39555. 2016.PubMed/NCBI View Article : Google Scholar

82 

Chen Y, Zhou X, Qiao J and Bao A: Autophagy is a regulator of TRAIL-induced apoptosis in NSCLC A549 cells. J Cell Commun Signal. 11:219–226. 2017.PubMed/NCBI View Article : Google Scholar

83 

Wechman SL, Rao XM, Gomez-Gutierrez JG, Zhou HS and McMasters KM: The role of JNK phosphorylation as a molecular target to enhance adenovirus replication, oncolysis and cancer therapeutic efficacy. Cancer Biol Ther. 19:1174–1184. 2018.PubMed/NCBI View Article : Google Scholar

84 

Wang Y, Xiong H, Liu D, Hill C, Ertay A, Li J, Zou Y, Miller P, White E, Downward J, et al: Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells. Autophagy. 15:886–899. 2019.PubMed/NCBI View Article : Google Scholar

85 

Bryant KL, Stalnecker CA, Zeitouni D, Klomp JE, Peng S, Tikunov AP, Gunda V, Pierobon M, Waters AM, George SD, et al: Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nat Med. 25:628–640. 2019.PubMed/NCBI View Article : Google Scholar

86 

Mou L, Liang B, Liu G, Jiang J, Liu J, Zhou B, Huang J, Zang N, Liao Y, Ye L, et al: Berbamine exerts anticancer effects on human colon cancer cells via induction of autophagy and apoptosis, inhibition of cell migration and MEK/ERK signalling pathway. J BUON. 24:1870–1875. 2019.PubMed/NCBI

87 

Tian Y, Song W, Li D, Cai L and Zhao Y: Resveratrol as a Natural regulator of autophagy for prevention and treatment of cancer. OncoTargets Ther. 12:8601–8609. 2019.PubMed/NCBI View Article : Google Scholar

88 

Sánchez-Martín P, Saito T and Komatsu M: p62/SQSTM1: ‘Jack of all trades’ in health and cancer. FEBS J. 286:8–23. 2019.PubMed/NCBI View Article : Google Scholar

89 

Li Y, Shi J, Qi S, Zhang J, Peng D, Chen Z, Wang G, Wang Z and Wang L: IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2. J Exp Clin Cancer Res. 37:196–227. 2018.PubMed/NCBI View Article : Google Scholar

90 

Panigrahi DP, Bhol CS, R N, Nagini S, Patil S, Maiti TK and Bhutia SK: Abrus agglutinin inhibits oral carcinogenesis through inactivation of NRF2 signaling pathway. Int J Biol Macromol. 9:1–31. 2019.PubMed/NCBI View Article : Google Scholar

91 

Yang L, Sun X, Ye Y, Lu Y, Zuo J, Liu W, Elcock A and Zhu S: p38α mitogen-activated protein kinase is a druggable target in pancreatic adenocarcinoma. Front Oncol. 9:1294–1314. 2019.PubMed/NCBI View Article : Google Scholar

92 

Patel PH, Pénalva C, Kardorff M, Roca M, Pavlović B, Thiel A, Teleman AA and Edgar BA: Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut. Nat Commun. 10:4365–4378. 2019.PubMed/NCBI View Article : Google Scholar

93 

Del Barco Barrantes I, Stephan-Otto Attolini C, Slobodnyuk K, Igea A, Gregorio S, Gawrzak S, Gomis RR and Nebreda AR: Regulation of mammary luminal cell fate and tumorigenesis by p38α. Stem Cell Reports. 10:257–271. 2018.PubMed/NCBI View Article : Google Scholar

94 

Mo'men YS, Hussein RM and Kandeil MA: A novel chemoprotective effect of tiopronin against diethylnitrosamine-induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK-P53 signalling cascade. Clin Exp Pharmacol Physiol. 47:322–332. 2020.PubMed/NCBI View Article : Google Scholar

95 

Aggarwal V, Tuli HS, Varol A, Thakral F, Yerer MB, Sak K, Varol M, Jain A, Khan MA and Sethi G: Role of reactive oxygen species in cancer progression: Molecular mechanisms and recent advancements. Biomolecules. 9:735–750. 2019.PubMed/NCBI View Article : Google Scholar

96 

Boldbaatar J, Gunarta IK, Suzuki R, Erdenebaatar P, Davaakhuu G, Hohjoh H and Yoshioka K: Protective role of c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP) in curcumin-induced cancer cell death. Biochem Biophys Res Commun. 29:1–31. 2019.PubMed/NCBI View Article : Google Scholar

97 

Shi Y, Liu Y, Zheng Y, Tang Y, Zhu G, Qiu W, Huang L, Han S, Yin J, Peng B, et al: Autophagy triggered by MAVS inhibits Coxsackievirus A16 replication. Acta Virol. 63:392–402. 2019.PubMed/NCBI View Article : Google Scholar

98 

Yuan YL, Jiang N, Li ZY, Song ZZ, Yang ZH, Xue WH, Zhang XJ and Du Y: Polyphyllin VI induces apoptosis and autophagy in human osteosarcoma cells by modulation of ROS/JNK activation. Drug Des Devel Ther. 13:3091–3103. 2019.PubMed/NCBI View Article : Google Scholar

99 

Zhao M, Gu L, Li Y, Chen S, You J, Fan L, Wang Y and Zhao L: Chitooligosaccharides display anti-tumor effects against human cervical cancer cells via the apoptotic and autophagic pathways. Carbohydr Polym. 224:115171–115184. 2019.PubMed/NCBI View Article : Google Scholar

100 

Cheng X, Tan S, Duan F, Yuan Q, Li Q and Deng G: Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM. Breast Cancer. 26:766–775. 2019.PubMed/NCBI View Article : Google Scholar

101 

Kim KY, Oh TW, Yang HJ, Kim YW, Ma JY and Park KI: Ethanol extract of Chrysanthemum zawadskii Herbich induces autophagy and apoptosis in mouse colon cancer cells through the regulation of reactive oxygen species. BMC Complement Altern Med. 19:274–283. 2019.PubMed/NCBI View Article : Google Scholar

102 

Wang F, Chen Y, Wang Y, Yin Y, Qu G, Song M and Wang H: Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells. Nanotoxicology. 13:543–557. 2019.PubMed/NCBI View Article : Google Scholar

103 

Chen G, Ding XF, Bouamar H, Pressley K and Sun LZ: Everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells. Am J Physiol Cell Physiol. 317:C244–C252. 2019.PubMed/NCBI View Article : Google Scholar

104 

Booth L, Roberts JL, Avogadri-Connors F, Cutler RE Jr, Lalani AS, Poklepovic A and Dent P: The irreversible ERBB1/2/4 inhibitor neratinib interacts with the BCL-2 inhibitor venetoclax to kill mammary cancer cells. Cancer Biol Ther. 19:239–247. 2018.PubMed/NCBI View Article : Google Scholar

105 

Zhou D, Dai L, Liu X, Que F, Xu Y, Luo X, Zhu Y, Liu S, Li Y and Yu L: Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells. Nan Fang Yi Ke Da Xue Xue Bao. 39:401–408. 2019.PubMed/NCBI View Article : Google Scholar : (In Chinese).

106 

Antonietti P, Gessler F, Düssmann H, Reimertz C, Mittelbronn M, Prehn JH and Kögel D: AT-101 simultaneously triggers apoptosis and a cytoprotective type of autophagy irrespective of expression levels and the subcellular localization of Bcl-xL and Bcl-2 in MCF7 cells. Biochim Biophys Acta. 1863:499–509. 2016.PubMed/NCBI View Article : Google Scholar

107 

Tong H, Li T, Qiu W and Zhu Z: Claudin-1 silencing increases sensitivity of liver cancer HepG2 cells to 5-fluorouracil by inhibiting autophagy. Oncol Lett. 18:5709–5716. 2019.PubMed/NCBI View Article : Google Scholar

108 

Lee J, Jung JH, Hwang J, Park JE, Kim JH, Park WY, Suh JY and Kim SH: CNOT2 is critically involved in atorvastatin induced apoptotic and autophagic cell death in non-small cell lung cancers. Cancers (Basel). 11:1470–1484. 2019.PubMed/NCBI View Article : Google Scholar

109 

Lee JE, Yoon SS and Moon EY: Curcumin-induced autophagy augments its antitumor effect against A172 human glioblastoma cells. Biomol Ther (Seoul). 27:484–491. 2019.PubMed/NCBI View Article : Google Scholar

110 

Silva VAO, Rosa MN, Tansini A, Martinho O, Tanuri A, Evangelista AF, Cruvinel Carloni A, Lima JP, Pianowski LF and Reis RM: Semi-synthetic ingenol derivative from euphorbia tirucalli inhibits protein kinase C isotypes and promotes autophagy and S-phase arrest on glioma cell lines. Molecules. 24:4265–4282. 2019.PubMed/NCBI View Article : Google Scholar

111 

Robke L, Laraia L, Carnero Corrales MA, Konstantinidis G, Muroi M, Richters A, Winzker M, Engbring T, Tomassi S, Watanabe N, et al: Phenotypic identification of a novel autophagy inhibitor chemotype targeting lipid kinase VPS34. Angew Chem Int Ed Engl. 56:8153–8157. 2017.PubMed/NCBI View Article : Google Scholar

112 

Carew JS, Espitia CM, Zhao W, Han Y, Visconte V, Phillips J and Nawrocki ST: Disruption of autophagic degradation with ROC-325 antagonizes renal cell carcinoma pathogenesis. Clin Cancer Res. 23:2869–2879. 2017.PubMed/NCBI View Article : Google Scholar

113 

Guntuku L, Gangasani JK, Thummuri D, Borkar RM, Manavathi B, Ragampeta S, Vaidya JR, Sistla R and Vegi NGM: IITZ-01, a novel potent lysosomotropic autophagy inhibitor, has single-agent antitumor efficacy in triple-negative breast cancer in vitro and in vivo. Oncogene. 38:581–595. 2018.PubMed/NCBI View Article : Google Scholar

114 

Wu MY, Wang SF, Cai CZ, Tan JQ, Li M, Lu JJ, Chen XP, Wang YT, Zheng W and Lu JH: Natural autophagy blockers, dauricine (DAC) and daurisoline (DAS), sensitize cancer cells to camptothecin-induced toxicity. Oncotarget. 8:77673–77684. 2017.PubMed/NCBI View Article : Google Scholar

115 

Zhao Y, Li K, Zhao B and Su L, Li K, Zhao B and Su L: HSP90 inhibitor DPB induces autophagy and more effectively apoptosis in A549 cells combined with autophagy inhibitors. In Vitro Cell Dev Biol Anim. 55:349–354. 2019.PubMed/NCBI View Article : Google Scholar

116 

Han J, Lv W, Sheng H, Wang Y, Cao L, Huang S, Zhu L and Hu J: Ecliptasaponin A induces apoptosis through the activation of ASK1/JNK pathway and autophagy in human lung cancer cells. Ann Transl Med. 7:539–560. 2019.PubMed/NCBI View Article : Google Scholar

117 

Polishchuk EV, Merolla A, Lichtmannegger J, Romano A, Indrieri A, Ilyechova EY, Concilli M, De Cegli R, Crispino R, Mariniello M, et al: Activation of autophagy, observed in liver tissues from patients with Wilson disease and from ATP7B-deficient animals, protects hepatocytes from copper-induced apoptosis. Gastroenterology. 156:1173–1189.e5. 2019.PubMed/NCBI View Article : Google Scholar

118 

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, et al: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12:1–222. 2016.PubMed/NCBI View Article : Google Scholar

119 

Xuan F, Huang M, Liu W, Ding H, Yang L and Cui H: Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1. Neuro-oncol. 18:819–829. 2016.PubMed/NCBI View Article : Google Scholar

120 

Du H, Che J, Shi M, Zhu L, Hang JB, Chen Z and Li H: Beclin 1 expression is associated with the occurrence and development of esophageal squamous cell carcinoma. Oncol Lett. 14:6823–6828. 2017.PubMed/NCBI View Article : Google Scholar

121 

Chu C, Niu X, Ou X and Hu C: LAPTM4B knockdown increases the radiosensitivity of EGFR-overexpressing radioresistant nasopharyngeal cancer cells by inhibiting autophagy. OncoTargets Ther. 12:5661–5677. 2019.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen C, Gao H and Su X: Autophagy-related signaling pathways are involved in cancer (Review). Exp Ther Med 22: 710, 2021.
APA
Chen, C., Gao, H., & Su, X. (2021). Autophagy-related signaling pathways are involved in cancer (Review). Experimental and Therapeutic Medicine, 22, 710. https://doi.org/10.3892/etm.2021.10142
MLA
Chen, C., Gao, H., Su, X."Autophagy-related signaling pathways are involved in cancer (Review)". Experimental and Therapeutic Medicine 22.1 (2021): 710.
Chicago
Chen, C., Gao, H., Su, X."Autophagy-related signaling pathways are involved in cancer (Review)". Experimental and Therapeutic Medicine 22, no. 1 (2021): 710. https://doi.org/10.3892/etm.2021.10142
Copy and paste a formatted citation
x
Spandidos Publications style
Chen C, Gao H and Su X: Autophagy-related signaling pathways are involved in cancer (Review). Exp Ther Med 22: 710, 2021.
APA
Chen, C., Gao, H., & Su, X. (2021). Autophagy-related signaling pathways are involved in cancer (Review). Experimental and Therapeutic Medicine, 22, 710. https://doi.org/10.3892/etm.2021.10142
MLA
Chen, C., Gao, H., Su, X."Autophagy-related signaling pathways are involved in cancer (Review)". Experimental and Therapeutic Medicine 22.1 (2021): 710.
Chicago
Chen, C., Gao, H., Su, X."Autophagy-related signaling pathways are involved in cancer (Review)". Experimental and Therapeutic Medicine 22, no. 1 (2021): 710. https://doi.org/10.3892/etm.2021.10142
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