ERBB3 Promotes Malignant Behaviors of Endometrial Cancer Cells with Involvement of the Ras-ERK/MAPK Signaling Pathway

Background: Endometrial cancer is a common gynecological malignancy, and elucidating its molecular basis may provide new clues for targeted intervention. This study investigated the role of ERBB3 in endometrial cancer cells and explored whether Ras-ERK/MAPK signaling is involved in ERBB3-mediated regulation. Methods: Bioinformatic screening was performed using public databases to identify candidate genes associated with endometrial cancer. ERBB3 was selected for further analysis. ERBB3 expression was evaluated in public datasets and examined in endometrial cancer cells. Loss-of-function experiments, rescue assays, Western blotting, and co-immunoprecipitation were used to assess the biological function and potential mechanism of ERBB3. Results: ERBB3 knockdown significantly inhibited proliferation, migration, and invasion, and promoted apoptosis in Ishikawa and RL95-2 cells. These changes were accompanied by decreased Ras-ERK/MAPK signaling. Moreover, Ras overexpression partially reversed the effects induced by ERBB3 knockdown. Co-immunoprecipitation suggested a molecular association between ERBB3 and Ras within a protein complex, but did not demonstrate direct physical binding. Conclusions: ERBB3 appears to promote malignant behaviors in endometrial cancer cells, and the Ras-ERK/MAPK pathway may be one of the downstream mechanisms involved. Further validation in additional experimental models and clinical samples is needed.