Family with sequence similarity 46 member a confers chemo-resistance to ovarian carcinoma via TGF-β/Smad2 signaling

Abstract

ABSTRACT Ovarian cancer is the most lethal malignancy with depressive 5-year survival rate, mainly due to patients with advanced stages experience tumor recurrence and resistance to the current chemotherapeutic agents. Thus, exploring the underlying molecular mechanisms involved in chemo-resistance is crucial for management of treatment to improve therapeutic outcomes. In the current study, we found overexpression of FAM46A in ovarian cancer patients demonstrated an aggressive phenotype and poor outcome. Furthermore, FAM46A overexpression in ovarian cancer cells induces higher CDDP resistance. However, inhibition of FAM46A sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Mechanically, upregulation of FAM46A activated transforming growth factor-β (TGF-β)/Smad signaling and upregulated the levels of nuclear Smad2. Taken together, our results highlight the important oncogenic role of FAM46A in ovarian cancer progression and might provide a potential clinical target for patients with chemo resistant ovarian cancer.