FAM72A promotes cervical cancer progression by regulating the PI3K pathway

Abstract

Cervical cancer (CC) is a major malignancy and a serious threat to women’s health worldwide. The role of FAM72A in CC remains poorly defined. This study aimed to investigate its function in CC progression and its impact on the PI3K/AKT/mTOR pathway. FAM72A expression in CC was examined using TCGA-CESC and GEO (GSE63514) datasets, and then validated in CC tissues and cell lines. Functional assays assessed cell proliferation (CCK-8, EdU), invasion (Transwell), apoptosis (flow cytometry), and epithelial–mesenchymal transition (EMT; Western blot for E-cadherin/N-cadherin). The role of FAM72A in the PI3K/AKT/mTOR pathway was further evaluated by Western blot and pharmacological modulation with the activator 740 Y-P and the inhibitor LY294002. In vivo, a xenograft model with BALB/c nude mice was used to assess tumor growth, apoptosis (TUNEL staining), proliferation (Ki-67 IHC), and pathway activation (p-PI3K, p-AKT, and p-mTOR). FAM72A expression was upregulated in CC tissues and correlated with poor survival. Subgroup analysis showed that high FAM72A expression was associated with advanced FIGO stage, lymph node metastasis, and deep stromal invasion, indicating a link with aggressive clinical features. FAM72A silencing suppressed proliferation and invasion but promoted apoptosis, mainly through inhibition of the PI3K/AKT/mTOR pathway. Conversely, FAM72A overexpression enhanced these malignant traits. In vivo, FAM72A knockdown reduced tumor burden and altered EMT markers and PI3K/AKT/mTOR pathway activity. FAM72A promotes CC progression, at least in part, through activation of the PI3K/AKT/mTOR pathway, supporting its value as a potential therapeutic target.