Recurrent PIK3CA-E545K mutation promotes cervical cancer growth and invasion via AKT/mTOR signaling.

Abstract

Cervical cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Although genomic alterations in oncogenic signaling pathways have been implicated in cervical carcinogenesis, the functional impact of recurrent driver mutations remains incompletely understood. Whole-exome sequencing was performed on paired tumor and matched non-tumor tissues from 61 patients to identify recurrent somatic alterations. Functional significance was subsequently evaluated using cervical cancer cell models through proliferation, invasion, apoptosis, and signaling pathway analyses. Tumorigenic potential was further assessed using a xenograft mouse model. Genomic profiling identified PIK3CA as one of the most frequently mutated genes in cervical cancer. Functional analyses demonstrated that PIK3CA E545K mutation (PIK3CA-E545K-MUT) significantly enhanced tumor cell proliferation and invasive capacity while suppressing apoptosis. Mechanistically, these effects were associated with sustained activation of the AKT/mTOR signaling pathway, as evidenced by increased phosphorylation of key downstream effectors. Consistently, in vivo xenograft experiments confirmed that PIK3CA-E545K-MUT-driven signaling activation promoted tumor growth. Our findings establish a functional and mechanistic link between recurrent PIK3CA-E545K-MUT and aggressive tumor behavior in cervical cancer via AKT/mTOR pathway activation. These results provide experimental support for targeting the PI3K/AKT/mTOR axis as a potential therapeutic strategy in cervical cancer.