Biomol Ther.  2019 Nov;27(6):591-602. 10.4062/biomolther.2019.063.

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

• Cho E
• Kwon YJ
• Ye DJ
• Baek HS
• Kwon TU
• Choi HK
• Chun YJ

• KMID: 2462887
• DOI: http://doi.org/10.4062/biomolther.2019.063

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.

Keyword

G0S2; FAK-Src signaling; Hippo pathway; EMT

MeSH Terms

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*
Cadherins
Lipase
RNA, Small Interfering