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RKIP and 14-3-3ε Exert an Opposite Effect on Human Gastric Cancer Cells SGC7901 by Regulating the ERK/MAPK Pathway Differently

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Abstract

Background

Raf-1 kinase inhibitor protein (RKIP) inhibits Raf (a key element in the ERK/MAPK pathway) and is regarded as anti-tumoral. In contrast, 14-3-3 is considered protumoral. However, the pathogenetic role of RKIP and 14-3-3ε in gastric cancer is unclear.

Aim

The purpose of this study was to examine the influence of 14-3-3ε and RKIP on SGC7901, the regulation of the ERK/MAKP pathway by both, and the interaction between the two proteins.

Methods

RKIP and 14-3-3ε genes were introduced into SGC7901 cells using gene cloning technique, then, the bioactivities including the proliferation, migration and invasion of the cells were assessed by MTT and migration assays. ERK/MAKP pathway’s activity was examined using real-time quantitative RT–PCR, western blot, immunoprecipitation and 3D-immunolocalization techniques.

Results

Our results showed that RKIP inhibited SGC7901 cells’ bioactivities whereas 14-3-3ε upregulated them through the involvement of the ERK/MAPK pathway. RKIP inactivated this pathway, but 14-3-3ε activated it. RKIP and 14-3-3ε were co-localized in the cells and interacted with each other; this attributed to their opposite influence on the ERK/MAPK pathway and the cells bioactivities.

Conclusions

The ERK/MAPK pathway is involved in the pathogenesis of gastric cancer; RKIP and 14-3-3ε exert an opposite effect on this pathway and the cells possibly via both direct and indirect reactions with the elements in this pathway. The interaction between RKIP and 14-3-3ε may also contribute to their pathogenetic roles in gastric cancer.

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References

  1. Alberts SR, Cervantes A, Velde CJH. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003;14:ii31–ii36.

    PubMed  Google Scholar 

  2. Seddiqi N, Bollengier F, Alliel PM, et al. Amino acid sequence of the Homo sapiens brain 21–23-kDa protein (neuropolypeptide h3), comparison with its counterparts from Rattus norvegicus and Bos taurus species, and expression of its mRNA in different tissues. J Mol Evol. 1994;39:655–660.

    Article  PubMed  CAS  Google Scholar 

  3. Odabaei G, Chatterjee D, Jazirehi AR, Goodglick L, Yeung K, Bonavida B. Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis. Adv Cancer Res. 2004;91:169–200.

    Article  PubMed  CAS  Google Scholar 

  4. Avruch J, Khokhlatchev A, Kyriakis JM, et al. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Prog Horm Res. 2001;56:127–155.

    Article  PubMed  CAS  Google Scholar 

  5. Hilger RA, Scheulen ME, Strumberg D. The Ras–Raf–MEK–ERK pathway in the treatment of cancer. Onkologie. 2002;25:511–518.

    Article  PubMed  CAS  Google Scholar 

  6. McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773:1263–1284.

    Article  PubMed  CAS  Google Scholar 

  7. Li HZ, Gao Y, Zhao XL, et al. Effects of Raf kinase inhibitor protein expression on metastasis and progression of human breast cancer. Mol Cancer Res. 2009;7:832–840.

    Article  PubMed  CAS  Google Scholar 

  8. Fu Z, Kitagawa Y, Shen R, et al. Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate. 2006;66:248–256.

    Article  PubMed  CAS  Google Scholar 

  9. Minoo P, Zlobec I, Baker K, et al. Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer. Am J Clin Pathol. 2007;127:820–827.

    Article  PubMed  Google Scholar 

  10. Zhang ZQ, Li MY, Zhang GY, et al. Identification of human gastric carcinoma biomarkers by differential protein expression analysis using 18O labeling and nano LC–MS/MS coupled with laser capture microdissection. Med Oncol. 2010;27:296–303.

    Article  PubMed  CAS  Google Scholar 

  11. Zuo S, Xue Y, Tang SW, et al. 14-3-3 epsilon dynamically interacts with key components of mitogen-activated protein kinase signal module for selective modulation of the TNF-α-induced time course-dependent NF-γB activity. J Proteome Res. 2010;9:3465–3478.

    Article  PubMed  CAS  Google Scholar 

  12. Chang HC, Rubin GM. 14-3-3ε positively regulates Ras-mediated signaling in Drosophila. Genes Dev. 1997;11:1132–1139.

    Article  PubMed  CAS  Google Scholar 

  13. Liou JY, Ghelani D, Yeh S, Wu KK. Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3ε. Cancer Res. 2007;67:3185–3191.

    Article  PubMed  CAS  Google Scholar 

  14. Chuthapisith S, Layfield R, Kerr ID, Hughes C, Eremin O. Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs. Int J Oncol. 2007;30:1545–1551.

    PubMed  CAS  Google Scholar 

  15. Seow TK, Ong SE, Liang RC, et al. Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell line, HCC-M, and identification of the separated proteins by mass spectrometry. Electrophoresis. 2000;21:1787–1813.

    Article  PubMed  CAS  Google Scholar 

  16. Gu H, Yan L, Li J, Zhang G. Characterization of interaction proteins for gastric cancer related novel protein RKIP. Prog Biochem Biophys. 2012;39:68–77.

    Article  CAS  Google Scholar 

  17. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001;410:37–40.

    Article  PubMed  CAS  Google Scholar 

  18. Chatterjee D, Bai Y, Wang Z, et al. RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem. 2004;279:17515–17523.

    Article  PubMed  CAS  Google Scholar 

  19. Liang S, Xu Y, Shen G, et al. Quantitative protein expression profiling of 14-3-3 isoforms in human renal carcinoma shows 14-3-3 epsilon is involved in limitedly increasing renal cell proliferation. Electrophoresis. 2009;30:4152–4162.

    Article  PubMed  CAS  Google Scholar 

  20. Liu Y, Song F, Wu WK, et al. Triptolide inhibits colon cancer cell proliferation and induces cleavage and translocation of 14-3-3 epsilon. Cell Biochem Funct. 2012;30(4):271–278.

    Google Scholar 

  21. Dabbous MK, Jefferson MM, Haney L, Thomas EL. Biomarkers of metastatic potential in cultured adenocarcinoma clones. Clin Exp Metastasis. 2011;28:101–111.

    Article  PubMed  CAS  Google Scholar 

  22. Marais R, Marshall CJ. Control of the ERK MAP kinase cascade by Ras and Raf. Cancer Surv. 1996;27:101–125.

    PubMed  CAS  Google Scholar 

  23. Yeung K, Seitz T, Li S, et al. Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999;401:173–177.

    Article  PubMed  CAS  Google Scholar 

  24. Yeung K, Janosch P, McFerran B, et al. Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol. 2000;20:3079–3085.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81072038).

Conflict of interest

No conflicts of interest of any kind exit in the submission of this manuscript.

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Authors and Affiliations

  1. Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha City, 410008, Hunan Province, People’s Republic of China

    Lu Yan, Huan Gu, Jia Li, Meihua Xu, Ting Liu, Yueming Shen, Bolin Chen & Guiying Zhang

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  1. Lu Yan
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  2. Huan Gu
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  3. Jia Li
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  4. Meihua Xu
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  5. Ting Liu
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  6. Yueming Shen
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  7. Bolin Chen
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  8. Guiying Zhang
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Correspondence to Guiying Zhang.

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Yan, L., Gu, H., Li, J. et al. RKIP and 14-3-3ε Exert an Opposite Effect on Human Gastric Cancer Cells SGC7901 by Regulating the ERK/MAPK Pathway Differently. Dig Dis Sci 58, 389–396 (2013). https://doi.org/10.1007/s10620-012-2341-y

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  • DOI: https://doi.org/10.1007/s10620-012-2341-y

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