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2014-April Volume 31 Issue 4

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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.

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International Journal of Oncology

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

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

Oncology Reports

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

Experimental and Therapeutic Medicine

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

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

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

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

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

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Article

Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2

  • Authors:
    • Zixuan Li
    • Lianyue Qu
    • Hongshan Zhong
    • Ke Xu
    • Xueshan Qiu
    • Enhua Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The First Affiliated Hospital of China Medical University and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 1707-1714
    |
    Published online on: February 24, 2014
       https://doi.org/10.3892/or.2014.3050
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Abstract

Mitogen-inducible gene-6 (Mig-6), an immediate early response gene, is a specific negative regulator of epidermal growth factor receptor (EGFR). Ablation of Mig-6 has been shown to induce tumor formation in various tissues, supporting the tumor suppressor function of Mig-6. However, little is known about the role of Mig-6 in non-small cell lung cancer (NSCLC) apoptosis, nor has the contribution of upregulated Mig-6 on biological behaviors of A549 and H157 cells previously been reported. The aim of the present study was to investigate the effects of exogenously transfected Mig-6 on proliferation, invasion and apoptosis of A549 and H157 cells and to identify novel underlying mechanisms of Mig-6-induced apoptosis. We used immunohistochemical staining to examine the expression of Mig-6 protein in NSCLC tissues. For evaluation of the prognostic value of Mig-6 expression to each clinicopathologic factor, Kaplan-Meier method and Cox's proportional hazards model were employed. Mig-6 low expression was correlated with a poor prognosis in patients with lung cancer. Patients with high expression of Mig-6 had a statistically significantly longer survival than those with low expression of Mig-6. Cox's regression analysis indicated that loss of Mig-6 expression was an independent, unfavorable prognostic factors. We utilized siRNA-targeting Mig-6 and Mig-6 overexpression plasmid to determine the effect of Mig-6 on lung cancer cells. Flow cytometry studies revealed Mig-6 overexpression promoted apoptosis in NSCLC cell lines. siRNA-mediated Mig-6 knockdown inhibited apoptosis of cancer cells, but this anti-apoptotic effect was abolished by inhibition of ERK. Upregulation of Mig-6 decreased the proliferation and invasive potential of transfected cells. Moreover, upregulation of Mig-6 inhibited proliferation and invasion of A549 and H157 cells. Collectively, our results showed that Mig-6 is a potential biomarker for evaluation of tumor prognosis of lung cancer. Mig-6 promotes apoptosis in lung cancer cells via the ERK pathway.
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1 

Zhang YW and Vande Woude GF: Mig-6, signal transduction, stress response and cancer. Cell Cycle. 6:507–513. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Ogunbiyi OA, Goodfellow PJ, Gagliardi G, et al: Prognostic value of chromosome 1p allelic loss in colon cancer. Gastroenterology. 113:761–766. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Koshikawa K, Nomoto S, Yamashita K, Ishigure K, Takeda S and Nakao A: Allelic imbalance at 1p36 in the pathogenesis of human hepatocellular carcinoma. Hepatogastroenterology. 51:186–191. 2004.PubMed/NCBI

4 

Tseng RC, Chang JW, Hsien FJ, et al: Genomewide loss of heterozygosity and its clinical associations in non small cell lung cancer. Int J Cancer. 117:241–247. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Jeong JW, Lee HS, Lee KY, et al: Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease. Proc Natl Acad Sci USA. 106:8677–8682. 2009. View Article : Google Scholar

6 

Ferby I, Reschke M, Kudlacek O, et al: Mig6 is a negative regulator of EGF receptor-mediated skin morphogenesis and tumor formation. Nat Med. 12:568–573. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Zhang YW, Staal B, Su Y, et al: Evidence that MIG-6 is a tumor-suppressor gene. Oncogene. 26:269–276. 2007.

8 

Jin N, Gilbert JL, Broaddus RR, Demayo FJ and Jeong JW: Generation of a Mig-6 conditional null allele. Genesis. 45:716–721. 2007.

9 

Anastasi S, Sala G, Huiping C, et al: Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB-2 oncogenic potency and favors resistance to Herceptin. Oncogene. 24:4540–4548. 2005.PubMed/NCBI

10 

Anastasi S, Fiorentino L, Fiorini M, et al: Feedback inhibition by RALT controls signal output by the ErbB network. Oncogene. 22:4221–4234. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Xu D, Makkinje A and Kyriakis JM: Gene 33 is an endogenous inhibitor of epidermal growth factor (EGF) receptor signaling and mediates dexamethasone-induced suppression of EGF function. J Biol Chem. 280:2924–2933. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Anastasi S, Baietti MF, Frosi Y, Alema S and Segatto O: The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression of the EGFR catalytic activity. Oncogene. 26:7833–7846. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Amatschek S, Koenig U, Auer H, et al: Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes. Cancer Res. 64:844–856. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Li Z, Dong Q, Wang Y, Qu L, Qiu X and Wang E: Downregulation of Mig-6 in nonsmall-cell lung cancer is associated with EGFR signaling. Mol Carcinog. 51:522–534. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Wu S, Xing W, Peng J, et al: Tumor transfected with CCL21 enhanced reactivity and apoptosis resistance of human monocyte-derived dendritic cells. Immunobiology. 213:417–426. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Ling YH, Liebes L, Jiang JD, et al: Mechanisms of proteasome inhibitor PS-341-induced G2-M-phase arrest and apoptosis in human non-small cell lung cancer cell lines. Clin Cancer Res. 9:1145–1154. 2003.PubMed/NCBI

17 

Kim JW, Ferris RL and Whiteside TL: Chemokine C receptor 7 expression and protection of circulating CD8+ T lymphocytes from apoptosis. Clin Cancer Res. 11:7901–7910. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Faber AC, Li D, Song Y, et al: Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition. Proc Natl Acad Sci USA. 106:19503–19508. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Liu Y, Yang Y, Ye YC, et al: Activation of ERK-p53 and ERK-mediated phosphorylation of Bcl-2 are involved in autophagic cell death induced by the c-Met inhibitor SU11274 in human lung cancer A549 cells. J Pharmacol Sci. 118:423–432. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Okamoto K, Okamoto I, Okamoto W, et al: Role of survivin in EGFR inhibitor-induced apoptosis in non-small cell lung cancers positive for EGFR mutations. Cancer Res. 70:10402–10410. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Lin CI, Du J, Shen WT, et al: Mitogen-inducible gene-6 is a multifunctional adaptor protein with tumor suppressor-like activity in papillary thyroid cancer. J Clin Endocrinol Metab. 96:E554–E565. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Reschke M, Ferby I, Stepniak E, et al: Mitogen-inducible gene-6 is a negative regulator of epidermal growth factor receptor signaling in hepatocytes and human hepatocellular carcinoma. Hepatology. 51:1383–1390. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Ruan DT, Warren RS, Moalem J, et al: Mitogen-inducible gene-6 expression correlates with survival and is an independent predictor of recurrence in BRAFV600E positive papillary thyroid cancers. Surgery. 144:908–914. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Ying H, Zheng H, Scott K, et al: Mig-6 controls EGFR trafficking and suppresses gliomagenesis. Proc Natl Acad Sci USA. 107:6912–6917. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Kim TH, Franco HL, Jung SY, et al: The synergistic effect of Mig-6 and Pten ablation on endometrial cancer development and progression. Oncogene. 29:3770–3780. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Ewings KE, Wiggins CM and Cook SJ: Bim and the pro-survival Bcl-2 proteins: opposites attract, ERK repels. Cell Cycle. 6:2236–2240. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Chen YR, Wang X, Templeton D, Davis RJ and Tan TH: The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and γ radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem. 271:31929–31936. 1996.

28 

Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 270:1326–1331. 1995. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li Z, Qu L, Zhong H, Xu K, Qiu X and Wang E: Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2. Oncol Rep 31: 1707-1714, 2014.
APA
Li, Z., Qu, L., Zhong, H., Xu, K., Qiu, X., & Wang, E. (2014). Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2. Oncology Reports, 31, 1707-1714. https://doi.org/10.3892/or.2014.3050
MLA
Li, Z., Qu, L., Zhong, H., Xu, K., Qiu, X., Wang, E."Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2". Oncology Reports 31.4 (2014): 1707-1714.
Chicago
Li, Z., Qu, L., Zhong, H., Xu, K., Qiu, X., Wang, E."Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2". Oncology Reports 31, no. 4 (2014): 1707-1714. https://doi.org/10.3892/or.2014.3050
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Qu L, Zhong H, Xu K, Qiu X and Wang E: Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2. Oncol Rep 31: 1707-1714, 2014.
APA
Li, Z., Qu, L., Zhong, H., Xu, K., Qiu, X., & Wang, E. (2014). Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2. Oncology Reports, 31, 1707-1714. https://doi.org/10.3892/or.2014.3050
MLA
Li, Z., Qu, L., Zhong, H., Xu, K., Qiu, X., Wang, E."Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2". Oncology Reports 31.4 (2014): 1707-1714.
Chicago
Li, Z., Qu, L., Zhong, H., Xu, K., Qiu, X., Wang, E."Low expression of Mig-6 is associated with poor survival outcome in NSCLC and inhibits cell apoptosis via ERK-mediated upregulation of Bcl-2". Oncology Reports 31, no. 4 (2014): 1707-1714. https://doi.org/10.3892/or.2014.3050
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