BCAM-AKT2 fusion protein promotes unfolded protein response driven oncogenic signaling in SKOV3 epithelial ovarian cancer cell line.

In view of the rapidly increasing evidence that gene fusion mutations are frequent drivers of cancer, a deeper understanding of the molecular and functional hallmarks of specific gene fusions in epithelial ovarian cancer (EOC) is essential. In this work we sought to identify the molecular signature of the BCAM-AKT2 fusion protein in ovarian cancer cell lines and to assess the biological impact of the novel fusion in these cells. Our in-vitro results show that the BCAM-AKT2 fusion protein is engaged in proliferative action within EOC cell lines. Furthermore, RNA-seq analysis shows that the effect of BCAM-AKT2 in SKOV3 cells is associated with activated unfolded protein response (UPR) and with the inhibition of interferon alpha and beta signaling pathways, pyropstosis and viral response in EOC cell lines. Overall, our results indicate that in SKOV3 cells, BCAM-AKT2 modulates the UPR signaling pathway, which is known to interact with oncogene and tumor suppressor networks during cancer development. These findings offer fresh insights suggesting that BCAM-AKT2 could serve as a promising target for therapeutic interventions in ovarian cancer.