FAM172A promotes epithelial ovarian cancer progression and induces platinum resistance via the PI3K/AKT pathway

Abstract

Abstract This study aimed to investigate the role of FAM172A in epithelial ovarian cancer (EOC), a highly lethal gynecological malignancy often diagnosed at late stages with limited treatment options. FAM172A expression was evaluated in EOC and normal ovarian tissues using western blotting and immunohistochemistry, and its association with patient prognosis, treatment response, and CA125 levels was assessed by multivariate regression analysis. Functional assays were performed to examine the effects of FAM172A on EOC cell proliferation, migration, and invasion. In vivo models were used to evaluate the influence of FAM172A on tumor growth, metastasis, and chemosensitivity. The underlying mechanism was explored by modulating the PI3K-Akt pathway with pharmacological inhibitors and activators. FAM172A was significantly upregulated in EOC tissues, and its elevated expression correlated with poor prognosis, chemotherapy resistance, and increased CA125 levels. Multivariate analysis identified FAM172A expression, platinum sensitivity, and CA125 as independent prognostic factors. In vitro, FAM172A promoted malignant behavior and conferred resistance to cisplatin. In vivo, knockdown of FAM172A suppressed tumor progression and enhanced the efficacy of cisplatin. Mechanistically, FAM172A exerted its effects through regulation of the PI3K-Akt pathway, and modulation of PI3K signaling rescued FAM172A-induced phenotypic changes. These findings highlight FAM172A as a critical promoter of EOC progression, associated with aggressive tumor characteristics and treatment failure. By activating the PI3K-Akt pathway, FAM172A represents a promising therapeutic target for EOC, potentially offering new strategies to improve patient outcomes, particularly in overcoming chemoresistance.