# Germ cell-specific gene 2 accelerates cell cycle in epithelial ovarian cancer by inhibiting GSK3α-p27 cascade

## TL;DR

This study shows that the GSG2 gene promotes the growth of epithelial ovarian cancer by accelerating the cell cycle through a specific protein pathway.

## Contribution

The study reveals a novel mechanism by which GSG2 accelerates cell cycle progression in ovarian cancer via the GSK3α-p27 cascade.

## Key findings

- GSG2 knockdown inhibits cell proliferation and induces G2/M phase arrest in ovarian cancer cells.
- GSG2 phosphorylates GSK3α at Ser21, reducing p27 expression and promoting cell cycle progression.
- Inhibiting GSK3α activity rescues the effects of GSG2 knockdown on cell cycle and p27 expression.

## Abstract

Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors with rapid growth potential and poor prognosis, however, the molecular mechanism underlying its outgrowth remained elusive. Germ cell-specific gene 2 (GSG2) was previously reported to be highly expressed in ovarian cancer and was essential for the growth of EOC. In this study, GSG2-knockdown cells and GSG2-overexpress cells were established through lentivirus-mediated transfection with Human ovarian cancer cells HO8910 and SKOV3. Knockdown of GSG2 inhibited cell proliferation and induced G2/M phase arrest in EOC. Interestingly, the expression of p27, a well-known regulator of the cell cycle showed a most significant increase after GSG2 knockdown. Further phosphorylation-protein array demonstrated the phosphorylation of GSK3αSer21 decreased in GSG2-knockdown cells to the most extent. Notably, inhibiting GSK3α activity effectively rescued GSG2 knockdown’s suppression on cell cycle as well as p27 expression in EOC. Our study substantiates that GSG2 is able to phosphorylate GSK3α at Ser21 and then leads to the reduction of p27 expression, resulting in cell cycle acceleration and cell proliferation promotion. Thus, GSG2 may have the potential to become a promising target in EOC.

The online version contains supplementary material available at 10.1007/s10735-024-10185-6.