G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells

Cho, Eunah; Kwon, Yeo-Jung; Ye, Dong-Jin; Baek, Hyoung-Seok; Kwon, Tae-Uk; Choi, Hyung-Kyoon; Chun, Young-Jin

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자료유형: 학술저널

저자정보: Cho, Eunah (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) Kwon, Yeo-Jung (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) Ye, Dong-Jin (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) Baek, Hyoung-Seok (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) Kwon, Tae-Uk (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) Choi, Hyung-Kyoon (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University) Chun, Young-Jin (College of Pharmacy and Center for Metareceptome Research, Chung-Ang University)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제27권 제6호

발행연도: 2019.1

수록면: 591 - 602 (12page)

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Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

#G0S2 #FAK-Src signaling #Hippo pathway #EMT

참고문헌 (50)

참고문헌 신청

Antalis, C. J / 2011 / Migration of MDA-MB-231 breast cancer cells depends on the availability of exogenous lipids and cholesterol esterification / Clin. Exp. Metastasis 28:733~741

Bao, Y / 2011 / Mammalian Hippo pathway : from development to cancer and beyond / J. Biochem 149:361~379

Canel, M / 2010 / Quantitative in vivo imaging of the effects of inhibiting integrin signaling via Src and FAK on cancer cell movement : effects on E-cadherin dynamics / Cancer Res 70:9413~9422

Cheishvili, D / 2015 / A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness / Oncotarget 6:33253~33268

Danen, E. H / 2001 / Fibronectin, integrins, and growth control / J. Cell. Physiol 189:1~13

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