G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells
10.4062/biomolther.2019.063
- Author:
Eunah CHO
1
;
Yeo Jung KWON
;
Dong Jin YE
;
Hyoung Seok BAEK
;
Tae Uk KWON
;
Hyung Kyoon CHOI
;
Young Jin CHUN
Author Information
1. College of Pharmacy and Center for Metareceptome Research, Chung-Ang University, Seoul 06974, Republic of Korea. yjchun@cau.ac.kr
- Publication Type:Original Article
- Keywords:
G0S2;
FAK-Src signaling;
Hippo pathway;
EMT
- MeSH:
Breast Neoplasms;
Breast;
Cadherins;
Cell Line;
Cell Proliferation;
Cell Survival;
Down-Regulation;
Humans;
Lipase;
Neoplasm Metastasis;
Oligonucleotide Array Sequence Analysis;
RNA, Small Interfering;
Signal Transduction
- From:Biomolecules & Therapeutics
2019;27(6):591-602
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 β-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.
