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
August-2015 Volume 47 Issue 2

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
August-2015 Volume 47 Issue 2

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

The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review)

  • Authors:
    • Hua-Fu Zhao
    • Jing Wang
    • Shing-Shun Tony To
  • View Affiliations / Copyright

    Affiliations: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, P.R. China, Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, P.R. China
  • Pages: 429-436
    |
    Published online on: June 16, 2015
       https://doi.org/10.3892/ijo.2015.3052
  • 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

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and c-Jun N-terminal kinase (JNK) pathway are responsible for regulating a variety of cellular processes including cell growth, migration, invasion and apoptosis. These two pathways are essential to the development and progression of tumors. The dual roles of JNK signaling in apoptosis and tumor development determine the different interactions between the PI3K/Akt and JNK pathways. Activation of PI3K/Akt signaling can inhibit stress- and cytokine-induced JNK activation through Akt antagonizing and the formation of the JIP1-JNK module, as well as the activities of upstream kinases ASK1, MKK4/7 and MLK. On the other hand, hyperactivation of Akt and JNK is also found in cancers that harbor EGFR overexpression or loss of PTEN. Understanding the activation mechanism of PI3K/Akt and JNK pathways, as well as the interplays between these two pathways in cancer may contribute to the identification of novel therapeutic targets. In the present report, we summarized the current understanding of the PI3K/Akt and JNK signaling networks, as well as their biological roles in cancers. In addition, the interactions and regulatory network between PI3K/Akt and JNK pathways in cancer were discussed.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Cantley LC: The phosphoinositide 3-kinase pathway. Science. 296:1655–1657. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Katso R, Okkenhaug K, Ahmadi K, White S, Timms J and Waterfield MD: Cellular function of phosphoinositide 3-kinases: Implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 17:615–675. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Vanhaesebroeck B and Alessi DR: The PI3K-PDK1 connection: More than just a road to PKB. Biochem J. 346:561–576. 2000. View Article : Google Scholar : PubMed/NCBI

4 

Toker A and Newton AC: Cellular signaling: Pivoting around PDK-1. Cell. 103:185–188. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Sarbassov DD, Ali SM and Sabatini DM: Growing roles for the mTOR pathway. Curr Opin Cell Biol. 17:596–603. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Vivanco I and Sawyers CL: The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2:489–501. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Sun H, Lesche R, Li DM, Liliental J, Zhang H, Gao J, Gavrilova N, Mueller B, Liu X and Wu H: PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci USA. 96:6199–6204. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Song MS, Salmena L and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 13:283–296. 2012.PubMed/NCBI

9 

Srividya MR, Thota B, Shailaja BC, Arivazhagan A, Thennarasu K, Chandramouli BA, Hegde AS and Santosh V: Homozygous 10q23/ PTEN deletion and its impact on outcome in glioblastoma: A prospective translational study on a uniformly treated cohort of adult patients. Neuropathology. 31:376–383. 2011. View Article : Google Scholar

10 

Chong ML, Loh M, Thakkar B, Pang B, Iacopetta B and Soong R: Phosphatidylinositol-3-kinase pathway aberrations in gastric and colorectal cancer: Meta-analysis, co-occurrence and ethnic variation. Int J Cancer. 134:1232–1238. 2014. View Article : Google Scholar

11 

Garcia-Dios DA, Lambrechts D, Coenegrachts L, Vandenput I, Capoen A, Webb PM, Ferguson K, Akslen LA, Claes B, Vergote I, et al; ANECS. High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma. Gynecol Oncol. 128:327–334. 2013. View Article : Google Scholar

12 

McConechy MK, Ding J, Senz J, Yang W, Melnyk N, Tone AA, Prentice LM, Wiegand KC, McAlpine JN, Shah SP, et al: Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Mod Pathol. 27:128–134. 2014. View Article : Google Scholar :

13 

Jin G, Kim MJ, Jeon HS, Choi JE, Kim DS, Lee EB, Cha SI, Yoon GS, Kim CH and Jung TH: PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers. Lung Cancer. 69:279–283. 2010. View Article : Google Scholar

14 

Kang-Park S and Lee YI and Lee YI: PTEN modulates insulin-like growth factor II (IGF-II)-mediated signaling; the protein phosphatase activity of PTEN downregulates IGF-II expression in hepatoma cells. FEBS Lett. 545:203–208. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Yi HK, Kim SY, Hwang PH, Kim CY, Yang DH, Oh Y and Lee DY: Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells. Biochem Biophys Res Commun. 330:760–767. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Oki E, Baba H, Tokunaga E, Nakamura T, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, et al: Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer. Int J Cancer. 117:376–380. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Tang JM, He QY, Guo RX and Chang XJ: Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 51:181–191. 2006. View Article : Google Scholar

18 

Vivanco I, Rohle D, Versele M, Iwanami A, Kuga D, Oldrini B, Tanaka K, Dang J, Kubek S, Palaskas N, et al: The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation. Proc Natl Acad Sci USA. 107:6459–6464. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Weston CR and Davis RJ: The JNK signal transduction pathway. Curr Opin Cell Biol. 19:142–149. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Bode AM and Dong Z: The functional contrariety of JNK. Mol Carcinog. 46:591–598. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Yang JY, Moulin N, van Bemmelen MX, Dubuis G, Tawadros T, Haefliger JA, Waeber G and Widmann C: Splice variant-specific stabilization of JNKs by IB1/JIP1. Cell Signal. 19:2201–2207. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Barr RK and Bogoyevitch MA: The c-Jun N-terminal protein kinase family of mitogen-activated protein kinases (JNK MAPKs). Int J Biochem Cell Biol. 33:1047–1063. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Tournier C, Dong C, Turner TK, Jones SN, Flavell RA and Davis RJ: MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes Dev. 15:1419–1426. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Haeusgen W, Herdegen T and Waetzig V: The bottleneck of JNK signaling: Molecular and functional characteristics of MKK4 and MKK7. Eur J Cell Biol. 90:536–544. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Leicht DT, Balan V, Kaplun A, Singh-Gupta V, Kaplun L, Dobson M and Tzivion G: Raf kinases: Function, regulation and role in human cancer. Biochim Biophys Acta. 1773:1196–1212. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K and Gotoh Y: Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 275:90–94. 1997. View Article : Google Scholar : PubMed/NCBI

28 

Sun BK, Kim JH, Nguyen HN, Oh S, Kim SY, Choi S, Choi HJ, Lee YJ and Song JJ: MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation. Oncol Rep. 25:537–544. 2011.

29 

Xu Z, Maroney AC, Dobrzanski P, Kukekov NV and Greene LA: The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol Cell Biol. 21:4713–4724. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Lopez-Ilasaca M: Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades. Biochem Pharmacol. 56:269–277. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Shaulian E: AP-1 - The Jun proteins: Oncogenes or tumor suppressors in disguise? Cell Signal. 22:894–899. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Whitmarsh AJ, Cavanagh J, Tournier C, Yasuda J and Davis RJ: A mammalian scaffold complex that selectively mediates MAP kinase activation. Science. 281:1671–1674. 1998. View Article : Google Scholar : PubMed/NCBI

33 

Whitmarsh AJ, Kuan CY, Kennedy NJ, Kelkar N, Haydar TF, Mordes JP, Appel M, Rossini AA, Jones SN, Flavell RA, et al: Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes Dev. 15:2421–2432. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Nihalani D, Meyer D, Pajni S and Holzman LB: Mixed lineage kinase-dependent JNK activation is governed by interactions of scaffold protein JIP with MAPK module components. EMBO J. 20:3447–3458. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Lin A: Activation of the JNK signaling pathway: Breaking the brake on apoptosis. BioEssays. 25:17–24. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Lin A and Dibling B: The true face of JNK activation in apoptosis. Aging Cell. 1:112–116. 2002. View Article : Google Scholar

37 

Besirli CG and Johnson EM Jr: JNK-independent activation of c-Jun during neuronal apoptosis induced by multiple DNA-damaging agents. J Biol Chem. 278:22357–22366. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Huntwork-Rodriguez S, Wang B, Watkins T, Ghosh AS, Pozniak CD, Bustos D, Newton K, Kirkpatrick DS and Lewcock JW: JNK-mediated phosphorylation of DLK suppresses its ubiquitination to promote neuronal apoptosis. J Cell Biol. 202:747–763. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Reno EM, Haughian JM, Jackson TA, Thorne AM and Bradford AP: c-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells. Apoptosis. 14:809–820. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Robitaille K, Daviau A, Lachance G, Couture JP and Blouin R: Calphostin C-induced apoptosis is mediated by a tissue trans-glutaminase-dependent mechanism involving the DLK/JNK signaling pathway. Cell Death Differ. 15:1522–1531. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Song J, Ko HS, Sohn EJ, Kim B, Kim JH, Kim HJ, Kim C, Kim JE and Kim SH: Inhibition of protein kinase C α/βII and activation of c-Jun NH2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer NCI-H460 cells. Bioorg Med Chem Lett. 24:1188–1191. 2014. View Article : Google Scholar : PubMed/NCBI

42 

Kim BJ, Ryu SW and Song BJ: JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem. 281:21256–21265. 2006. View Article : Google Scholar : PubMed/NCBI

43 

Ambacher KK, Pitzul KB, Karajgikar M, Hamilton A, Ferguson SS and Cregan SP: The JNK- and AKT/GSK3β-signaling pathways converge to regulate Puma induction and neuronal apoptosis induced by trophic factor deprivation. PLoS One. 7:e468852012. View Article : Google Scholar

44 

Zhao Z, Wang J, Tang J, Liu X, Zhong Q, Wang F, Hu W, Yuan Z, Nie C and Wei Y: JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant ovarian cancer cells. Biochem J. 444:291–301. 2012. View Article : Google Scholar : PubMed/NCBI

45 

Yu J and Zhang L: PUMA, a potent killer with or without p53. Oncogene. 27(Suppl 1): S71–S83. 2008. View Article : Google Scholar

46 

Buschmann T, Potapova O, Bar-Shira A, Ivanov VN, Fuchs SY, Henderson S, Fried VA, Minamoto T, Alarcon-Vargas D, Pincus MR, et al: Jun NH2-terminal kinase phosphorylation of p53 on Thr-81 is important for p53 stabilization and transcriptional activities in response to stress. Mol Cell Biol. 21:2743–2754. 2001. View Article : Google Scholar : PubMed/NCBI

47 

Jones EV, Dickman MJ and Whitmarsh AJ: Regulation of p73-mediated apoptosis by c-Jun N-terminal kinase. Biochem J. 405:617–623. 2007. View Article : Google Scholar : PubMed/NCBI

48 

Yu C, Minemoto Y, Zhang J, Liu J, Tang F, Bui TN, Xiang J and Lin A: JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Mol Cell. 13:329–340. 2004. View Article : Google Scholar : PubMed/NCBI

49 

Nishina H, Fischer KD, Radvanyi L, Shahinian A, Hakem R, Rubie EA, Bernstein A, Mak TW, Woodgett JR and Penninger JM: Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3. Nature. 385:350–353. 1997. View Article : Google Scholar : PubMed/NCBI

50 

Potapova O, Gorospe M, Dougherty RH, Dean NM, Gaarde WA and Holbrook NJ: Inhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p53-dependent manner. Mol Cell Biol. 20:1713–1722. 2000. View Article : Google Scholar : PubMed/NCBI

51 

Cellurale C, Sabio G, Kennedy NJ, Das M, Barlow M, Sandy P, Jacks T and Davis RJ: Requirement of c-Jun NH(2)-terminal kinase for Ras-initiated tumor formation. Mol Cell Biol. 31:1565–1576. 2011. View Article : Google Scholar : PubMed/NCBI

52 

Xiao L and Lang W: A dominant role for the c-Jun NH2-terminal kinase in oncogenic ras-induced morphologic transformation of human lung carcinoma cells. Cancer Res. 60:400–408. 2000.PubMed/NCBI

53 

Nielsen C, Thastrup J, Bøttzauw T, Jäättelä M and Kallunki T: c-Jun NH2-terminal kinase 2 is required for Ras transformation independently of activator protein 1. Cancer Res. 67:178–185. 2007. View Article : Google Scholar : PubMed/NCBI

54 

Mathiasen DP, Egebjerg C, Andersen SH, Rafn B, Puustinen P, Khanna A, Daugaard M, Valo E, Tuomela S, Bøttzauw T, et al: Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation. Oncogene. 31:390–401. 2012. View Article : Google Scholar

55 

Johnson R, Spiegelman B, Hanahan D and Wisdom R: Cellular transformation and malignancy induced by ras require c-jun. Mol Cell Biol. 16:4504–4511. 1996.PubMed/NCBI

56 

Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, Ogura K, Karin M and Omata M: c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice. Cancer Res. 68:5031–5039. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Chang Q, Chen J, Beezhold KJ, Castranova V, Shi X and Chen F: JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma. Mol Cancer. 8:642009. View Article : Google Scholar : PubMed/NCBI

58 

Wang X, Chao L, Li X, Ma G, Chen L, Zang Y and Zhou G: Elevated expression of phosphorylated c-Jun NH2-terminal kinase in basal-like and ‘triple-negative’ breast cancers. Hum Pathol. 41:401–406. 2010. View Article : Google Scholar

59 

Li JY and Wang H, May S, Song X, Fueyo J, Fuller GN and Wang H: Constitutive activation of c-Jun N-terminal kinase correlates with histologic grade and EGFR expression in diffuse gliomas. J Neurooncol. 88:11–17. 2008. View Article : Google Scholar : PubMed/NCBI

60 

Takahashi R, Hirata Y, Sakitani K, Nakata W, Kinoshita H, Hayakawa Y, Nakagawa H, Sakamoto K, Hikiba Y, Ijichi H, et al: Therapeutic effect of c-Jun N-terminal kinase inhibition on pancreatic cancer. Cancer Sci. 104:337–344. 2013. View Article : Google Scholar

61 

Chen P, O’Neal JF, Ebelt ND, Cantrell MA, Mitra S, Nasrazadani A, Vandenbroek TL, Heasley LE and Van Den Berg CL: Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model. PLoS One. 5:e104432010. View Article : Google Scholar : PubMed/NCBI

62 

Das M, Garlick DS, Greiner DL and Davis RJ: The role of JNK in the development of hepatocellular carcinoma. Genes Dev. 25:634–645. 2011. View Article : Google Scholar : PubMed/NCBI

63 

Kennedy NJ, Sluss HK, Jones SN, Bar-Sagi D, Flavell RA and Davis RJ: Suppression of Ras-stimulated transformation by the JNK signal transduction pathway. Genes Dev. 17:629–637. 2003. View Article : Google Scholar : PubMed/NCBI

64 

Hübner A, Mulholland DJ, Standen CL, Karasarides M, Cavanagh-Kyros J, Barrett T, Chi H, Greiner DL, Tournier C, Sawyers CL, et al: JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate. Proc Natl Acad Sci USA. 109:12046–12051. 2012. View Article : Google Scholar : PubMed/NCBI

65 

Ying J, Li H, Cui Y, Wong AH, Langford C and Tao Q: Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/FAP-1 in multiple lymphomas and carcinomas through hypermethylation of a common bidirectional promoter. Leukemia. 20:1173–1175. 2006. View Article : Google Scholar : PubMed/NCBI

66 

Yoshida S, Fukino K, Harada H, Nagai H, Imoto I, Inazawa J, Takahashi H, Teramoto A and Emi M: The c-Jun NH2-terminal kinase3 (JNK3) gene: Genomic structure, chromosomal assignment, and loss of expression in brain tumors. J Hum Genet. 46:182–187. 2001. View Article : Google Scholar : PubMed/NCBI

67 

Jurewicz A, Matysiak M, Tybor K and Selmaj K: TNF-induced death of adult human oligodendrocytes is mediated by c-jun NH2-terminal kinase-3. Brain. 126:1358–1370. 2003. View Article : Google Scholar : PubMed/NCBI

68 

Dajas-Bailador F, Bantounas I, Jones EV and Whitmarsh AJ: Regulation of axon growth by the JIP1-AKT axis. J Cell Sci. 127:230–239. 2014. View Article : Google Scholar :

69 

Kim AH, Sasaki T and Chao MV: JNK-interacting protein 1 promotes Akt1 activation. J Biol Chem. 278:29830–29836. 2003. View Article : Google Scholar : PubMed/NCBI

70 

Pan J, Pei DS, Yin XH, Hui L and Zhang GY: Involvement of oxidative stress in the rapid Akt1 regulating a JNK scaffold during ischemia in rat hippocampus. Neurosci Lett. 392:47–51. 2006. View Article : Google Scholar

71 

Kim AH, Yano H, Cho H, Meyer D, Monks B, Margolis B, Birnbaum MJ and Chao MV: Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron. 35:697–709. 2002. View Article : Google Scholar : PubMed/NCBI

72 

Cerezo A, Martínez-A C, Lanzarot D, Fischer S, Franke TF and Rebollo A: Role of Akt and c-Jun N-terminal kinase 2 in apoptosis induced by interleukin-4 deprivation. Mol Biol Cell. 9:3107–3118. 1998. View Article : Google Scholar : PubMed/NCBI

73 

Levresse V, Butterfield L, Zentrich E and Heasley LE: Akt negatively regulates the cJun N-terminal kinase pathway in PC12 cells. J Neurosci Res. 62:799–808. 2000. View Article : Google Scholar : PubMed/NCBI

74 

Okubo Y, Blakesley VA, Stannard B, Gutkind S and Le Roith D: Insulin-like growth factor-I inhibits the stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem. 273:25961–25966. 1998. View Article : Google Scholar : PubMed/NCBI

75 

Wang Q, Zhang QG, Wu DN, Yin XH and Zhang GY: Neuroprotection of selenite against ischemic brain injury through negatively regulating early activation of ASK1/JNK cascade via activation of PI3K/AKT pathway. Acta Pharmacol Sin. 28:19–27. 2007. View Article : Google Scholar

76 

Kim AH, Khursigara G, Sun X, Franke TF and Chao MV: Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol. 21:893–901. 2001. View Article : Google Scholar : PubMed/NCBI

77 

Aikin R, Maysinger D and Rosenberg L: Cross-talk between phosphatidylinositol 3-kinase/AKT and c-jun NH2-terminal kinase mediates survival of isolated human islets. Endocrinology. 145:4522–4531. 2004. View Article : Google Scholar : PubMed/NCBI

78 

Xie D, Gore C, Zhou J, Pong RC, Zhang H, Yu L, Vessella RL, Min W and Hsieh JT: DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis. Proc Natl Acad Sci USA. 106:19878–19883. 2009. View Article : Google Scholar : PubMed/NCBI

79 

Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS and Choi EJ: Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation. J Biol Chem. 277:2573–2578. 2002. View Article : Google Scholar

80 

Murakami T, Takagi H, Suzuma K, Suzuma I, Ohashi H, Watanabe D, Ojima T, Suganami E, Kurimoto M, Kaneto H, et al: Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells. J Biol Chem. 280:31841–31849. 2005. View Article : Google Scholar : PubMed/NCBI

81 

Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR and Rana A: Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival. J Biol Chem. 278:3897–3902. 2003. View Article : Google Scholar

82 

Wen XR, Li C, Zong YY, Yu CZ, Xu J, Han D and Zhang GY: Dual inhibitory roles of geldanamycin on the c-Jun NH2-terminal kinase 3 signal pathway through suppressing the expression of mixed-lineage kinase 3 and attenuating the activation of apoptosis signal-regulating kinase 1 via facilitating the activation of Akt in ischemic brain injury. Neuroscience. 156:483–497. 2008. View Article : Google Scholar : PubMed/NCBI

83 

Song JJ and Lee YJ: Dissociation of Akt1 from its negative regulator JIP1 is mediated through the ASK1-MEK-JNK signal transduction pathway during metabolic oxidative stress: A negative feedback loop. J Cell Biol. 170:61–72. 2005. View Article : Google Scholar : PubMed/NCBI

84 

Logan SK, Falasca M, Hu P and Schlessinger J: Phosphatidylinositol 3-kinase mediates epidermal growth factor-induced activation of the c-Jun N-terminal kinase signaling pathway. Mol Cell Biol. 17:5784–5790. 1997.PubMed/NCBI

85 

Vivanco I, Palaskas N, Tran C, Finn SP, Getz G, Kennedy NJ, Jiao J, Rose J, Xie W, Loda M, et al: Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN. Cancer Cell. 11:555–569. 2007. View Article : Google Scholar : PubMed/NCBI

86 

Cui J, Han SY, Wang C, Su W, Harshyne L, Holgado-Madruga M and Wong AJ: c-Jun NH(2)-terminal kinase 2alpha2 promotes the tumorigenicity of human glioblastoma cells. Cancer Res. 66:10024–10031. 2006. View Article : Google Scholar : PubMed/NCBI

87 

Tsuiki H, Tnani M, Okamoto I, Kenyon LC, Emlet DR, Holgado-Madruga M, Lanham IS, Joynes CJ, Vo KT and Wong AJ: Constitutively active forms of c-Jun NH2-terminal kinase are expressed in primary glial tumors. Cancer Res. 63:250–255. 2003.PubMed/NCBI

88 

Nitta RT, Del Vecchio CA, Chu AH, Mitra SS, Godwin AK and Wong AJ: The role of the c-Jun N-terminal kinase 2-α-isoform in non-small cell lung carcinoma tumorigenesis. Oncogene. 30:234–244. 2011. View Article : Google Scholar

89 

Antonyak MA, Kenyon LC, Godwin AK, James DC, Emlet DR, Okamoto I, Tnani M, Holgado-Madruga M, Moscatello DK and Wong AJ: Elevated JNK activation contributes to the pathogenesis of human brain tumors. Oncogene. 21:5038–5046. 2002. View Article : Google Scholar : PubMed/NCBI

90 

Bost F, McKay R, Bost M, Potapova O, Dean NM and Mercola D: The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells. Mol Cell Biol. 19:1938–1949. 1999.PubMed/NCBI

91 

Rong Y, Belozerov VE, Tucker-Burden C, Chen G, Durden DL, Olson JJ, Van Meir EG, Mackman N and Brat DJ: Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/activator protein-1 transcriptional activity. Cancer Res. 69:2540–2549. 2009. View Article : Google Scholar : PubMed/NCBI

92 

Bonavia R, Inda MM, Vandenberg S, Cheng SY, Nagane M, Hadwiger P, Tan P, Sah DW, Cavenee WK and Furnari FB: EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway. Oncogene. 31:4054–4066. 2012. View Article : Google Scholar

93 

Gu J, Tamura M and Yamada KM: Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. J Cell Biol. 143:1375–1383. 1998. View Article : Google Scholar : PubMed/NCBI

94 

Hettinger K, Vikhanskaya F, Poh MK, Lee MK, de Belle I, Zhang JT, Reddy SA and Sabapathy K: c-Jun promotes cellular survival by suppression of PTEN. Cell Death Differ. 14:218–229. 2007. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao H, Wang J and Tony To S: The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review). Int J Oncol 47: 429-436, 2015.
APA
Zhao, H., Wang, J., & Tony To, S. (2015). The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review). International Journal of Oncology, 47, 429-436. https://doi.org/10.3892/ijo.2015.3052
MLA
Zhao, H., Wang, J., Tony To, S."The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review)". International Journal of Oncology 47.2 (2015): 429-436.
Chicago
Zhao, H., Wang, J., Tony To, S."The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review)". International Journal of Oncology 47, no. 2 (2015): 429-436. https://doi.org/10.3892/ijo.2015.3052
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao H, Wang J and Tony To S: The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review). Int J Oncol 47: 429-436, 2015.
APA
Zhao, H., Wang, J., & Tony To, S. (2015). The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review). International Journal of Oncology, 47, 429-436. https://doi.org/10.3892/ijo.2015.3052
MLA
Zhao, H., Wang, J., Tony To, S."The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review)". International Journal of Oncology 47.2 (2015): 429-436.
Chicago
Zhao, H., Wang, J., Tony To, S."The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review)". International Journal of Oncology 47, no. 2 (2015): 429-436. https://doi.org/10.3892/ijo.2015.3052
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