SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3

Molecular Medicine Reports

Volumn 12, Issue 1, 2015, Pages 83-92

  Wan, Jun ^a   Che, Yun ^a   Kang, Ningning ^a   Wu, Wei ^a  

^a ANHUI MEDICAL UNIVERSITY   (China)

Author keywords

Akt; Angiogenesis potential; Hypoxia inducible factor 1 ; Proliferation; Signal transducer and activator of transcription 3; Small cell lung cancer NCI H446 cells; Suppressor of cytokine signaling 3; Vascular endothelial growth factor A

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MESSENGER RNA; PROTEIN KINASE B; STAT3 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 3; HIF1A PROTEIN, HUMAN; PHOSPHATIDYLINOSITOL 3 KINASE; SOCS3 PROTEIN, HUMAN; SUPPRESSOR OF CYTOKINE SIGNALING;

ANGIOGENESIS; ARTICLE; CANCER INHIBITION; CELL PROLIFERATION; DEMETHYLATION; DOWN REGULATION; ENZYME ACTIVATION; HUMAN; HUMAN CELL; LUNG CANCER CELL LINE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; SMALL CELL LUNG CANCER; UPREGULATION; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; TUMOR CELL LINE;

CELL LINE, TUMOR; CELL PROLIFERATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; SMALL CELL LUNG CARCINOMA; STAT3 TRANSCRIPTION FACTOR; SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS;

EID: 84926668833     PISSN: 17912997     EISSN: 17913004     Source Type: Journal    
DOI: 10.3892/mmr.2015.3368     Document Type: Article

References (35)

1. Wan J, Ma J, Mei J and Shan G: The effects of HIF-1alpha on gene expression profiles of NCI-H446 human small cell lung cancer cells. J Exp Clin Cancer Res 28: 150, 2009.
2. Wan J, Chai H, Yu Z, et al: HIF-1alpha effects on angiogenic potential in human small cell lung carcinoma. J Exp Clin Cancer Res 30: 77, 2011.
3. Lee GW, Go SI, Cho YJ, et al: Hypoxia-inducible factor-1alpha and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: a retrospective study. J Thorac Oncol 7: 528-534, 2012.
4. Ioannou M, Papamichali R, Kouvaras E, et al: Hypoxia inducible factor-1 alpha and vascular endothelial growth factor in biopsies of small cell lung carcinoma. Lung 187: 321-329, 2009.
5. Zhang W, Zhang H and Xing L: Antisense oligonucleotide of hypoxia-inducible factor-1alpha suppresses growth and tumorigenicity of lung cancer cells A549. J Huazhong Univ Sci Technolog Med Sci 26: 448-450, 2006.
6. Lee JW, Bae SH, Jeong JW, Kim SH and Kim KW: Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp Mol Med 36: 1-12, 2004.
7. Kappler M, Taubert H, Schubert J, Vordermark D and Eckert AW: The real face of HIF1alpha in the tumor process. Cell Cycle 11: 3932-3936, 2012.
8. Park KW, Nozell SE and Benveniste EN: Protective role of STAT3 in NMDA and glutamate-induced neuronal death: negative regulatory effect of SOCS3. PLoS One 7: e50874, 2012.
9. Zhang S, Guo D, Jiang L, Zhang Q, Qiu X and Wang E: SOCS3 inhibiting migration of A549 cells correlates with PYK2 signaling in vitro. BMC Cancer 8: 150, 2008.
10. Baltayiannis G, Baltayiannis N and Tsianos EV: Suppressors of cytokine signaling as tumor repressors. Silencing of SOCS3 facilitates tumor formation and growth in lung and liver. J BUON 13: 263-265, 2008.
11. Tokita T, Maesawa C, Kimura T, et al: Methylation status of the SOCS3 gene in human malignant melanomas. Int J Oncol 30: 689-694, 2007.
12. Tischoff I, Hengge UR, Vieth M, et al: Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma. Gut 56: 1047-1053, 2007.
13. Yu ZB, Bai L, Qian P, et al: Restoration of SOCS3 suppresses human lung adenocarcinoma cell growth by downregulating activation of Erk1/2, Akt apart from STAT3. Cell Biol Int 33: 995-1001, 2009.
14. Tokunaga E, Oki E, Egashira A, et al: Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets 8: 27-36, 2008.
15. Dillon RL, White DE and Muller WJ: The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer. Oncogene 26: 1338-1345, 2007.
16. Campbell IG, Russell SE, Choong DY, et al: Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64: 7678-7681, 2004.
17. Zhang T, Cui GB, Zhang J, et al: Inhibition of PI3 kinases enhances the sensitivity of non-small cell lung cancer cells to ionizing radiation. Oncol Rep 24: 1683-1689, 2010.
18. Littlefield SL, Baird MC, Anagnostopoulou A and Raptis L: Synthesis, characterization and Stat3 inhibitory properties of the prototypical platinum(IV) anticancer drug, [PtCl3(NO2)(NH3)2] (CPA-7). Inorg Chem 47: 2798-2804, 2008.
19. Xu Q, Briggs J, Park S, et al: Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 24: 5552-5560, 2005.
20. Weber A, Hengge UR, Bardenheuer W, et al: SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. Oncogene 24: 6699-6708, 2005.
21. Liu Q, Li G, Li R, et al: IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J Neurooncol 100: 165-176, 2010.
22. Kumar K, Wigfield S, Gee HE, et al: Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse zenografts. J Mol Med (Berl) 91: 749-758, 2013.
23. Kimbro KS and Simons JW: Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr Relat Cancer 13: 739-749, 2006.
24. Fraga A, Ribeiro R and Medeiros R: Tumor hypoxia: the role of HIF. Actas Urol Esp 33: 941-951, 2009 (In Spanish).
25. Shi YH and Fang WG: Hypoxia-inducible factor-1 in tumour angiogenesis. World J Gastroenterol 10: 1082-1087, 2004.
26. Fan LF, Diao LM, Chen DJ, et al: Expression of HIF-1 alpha and its relationship to apoptosis and proliferation in lung cancer. Ai Zheng 21: 254-258, 2002 (In Chinese).
27. Zhang S, Wang W, Wang E and Qiu X: SOCS3 expression is inversely correlated with Pyk2 in non-small cell lung cancer and exogenous SOCS3 inhibits proliferation and invasion of A549 cells. Pathology 44: 434-440, 2012.
28. He B, You L, Uematsu K, et al: SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer. Proc Natl Acad Sci USA 100: 14133-14138, 2003.
29. Shouda T, Hiraoka K, Komiya S, et al: Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells. Cancer Lett 231: 176-184, 2006.
30. Yokogami K, Yamashita S and Takeshima H: Hypoxia-induced decreases in SOCS3 increase STAT3 activation and upregulate VEGF gene expression. Brain Tumor Pathol 30: 135-143, 2013.
31. Shen A, Chen Y, Hong F, et al: Pien Tze Huang suppresses IL-6-inducible STAT3 activation in human colon carcinoma cells through induction of SOCS3. Oncol Rep 28: 2125-2130, 2012.
32. Francipane MG, Eterno V, Spina V, et al: Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy. Cancer Res 69: 6141-6148, 2009.
33. Yu H and Jove R: The STATs of cancer - new molecular targets come of age. Nat Rev Cancer 4: 97-105, 2004.
34. Yamasaki M, Nomura T, Sato F and Mimata H: Chronic hypoxia induces androgen-independent and invasive behavior in LNCaP human prostate cancer cells. Urol Oncol 31: 1124-1131, 2013.
35. Yang CL, Liu YY, Ma YG, et al: Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS One 7: e37960, 2012.