CEBPB regulates ERK1/2 activity through SOS1 and contributes to ovarian cancer progression.

Abstract

Ovarian cancer (OC) is among the most prevalent malignant tumors affecting the female reproductive system. Notably, CEBPB has emerged as a highly promising biomarker, attracting substantial attention for its role in mediating chemotherapy resistance to PARP inhibitors (PARPi). However, the precise mechanism of action of CEBPB in OC remains poorly understood. CCK-8 assays, colony formation assays, transwell assays, and wound healing assays were employed to assess malignant behaviors of OC cells. Flow cytometry was utilized to analyze cell apoptosis and cell cycle progression. qRT-PCR and Western blot analyses were performed to quantify the levels of SOS1 and phosphorylated ERK1/2 (p-ERK1/2). Overexpression of CEBPB enhanced the proliferation, colony formation ability, invasion, migration, and cell cycle progression of SKOV3 and A2780 OC cells, while simultaneously inhibiting their apoptosis. Conversely, knockdown of CEBPB produced opposite effects (p < 0.01). Results from the MAPK Signaling Pathway PCR Array and Western blot analyses indicated that CEBPB increases the expression of SOS1 (p < 0.01). Additionally, dual-luciferase reporter assays demonstrated that CEBPB binds to the promoter sequence of the target gene SOS1. CEBPB knockdown significantly inhibited the malignant behavior of OC cells and reduced the levels of p-ERK1/2, whereas overexpression of SOS1 partially reversed this effect (p < 0.01). In xenograft models, CEBPB activates ERK1/2 via SOS1 upregulation, which subsequently promotes tumor growth and suppresses apoptosis (p < 0.01). CEBPB regulates ERK1/2 activity through SOS1 and contributes to OC progression.