ESCO2 drives breast cancer proliferation and metastasis through PI3K/AKT/mTOR phosphorylation: A potential therapeutic target

Abstract

Breast cancer remains a major global health threat to women, underscoring the urgent need for novel therapeutic targets. While ESCO2, an essential cell cycle regulator, has been implicated in cancer progression, its precise role and molecular mechanisms in breast cancer remain poorly understood. In this study, we first demonstrated significant upregulation of ESCO2 in breast cancer through analysis of TCGA and GEO datasets, which was further validated in clinical specimens and cell lines, with its expression correlating with advanced T-stage, aggressive molecular subtypes and poor prognosis. Functional studies in MDA-MB-231 and MDA-MB-468 cells revealed that ESCO2 overexpression promoted cell proliferation, migration and invasion, while its knockdown exerted opposite effects. Mechanistic investigations uncovered that ESCO2 depletion reduced phosphorylation of PI3K/AKT/mTOR pathway components, and co-immunoprecipitation assays confirmed direct interaction between ESCO2 and PI3K. Importantly, the tumor-suppressive effects of ESCO2 knockdown could be rescued by SC79-mediated AKT activation. In vivo experiments using xenograft mouse models consistently showed that ESCO2 silencing significantly inhibited tumor growth, increased apoptosis and necrosis, and reduced metastasis. Collectively, our findings establish ESCO2 as a novel oncogene driving breast cancer progression through PI3K/AKT/mTOR pathway activation, highlighting its potential as a promising therapeutic target for breast cancer intervention.