ESRP1 drives subtype-specific breast cancer progression through ER-regulated transcriptional programs and EMT-related splicing switch.

Abstract

Epithelial Splicing Regulatory Protein 1 (ESRP1), an epithelial splicing regulator, influences the invasiveness and metastasis of breast cancer cells, yet its prognostic significance and interaction with estrogen receptors are not fully understood. Our findings indicate that ESRP1 is significantly up-regulated in breast cancer tissues and correlates positively with adverse clinical outcomes, particularly in estrogen receptor (ER) positive breast cancer. In vitro experiments with cells demonstrated a dual regulatory mechanism: in ER-positive breast cancer cells, reduced expression of ESRP1 suppresses tumor cell proliferation but does not significantly affect tumor cell invasion and migration; conversely, in ER-negative breast cancer cells, ESRP1 hinders tumor progression by regulating the alternative splicing of epithelial-mesenchymal transition (EMT)-related genes. To investigate whether the presence of ER is a decisive factor in ESRP1's role, we treated ER-positive breast cancer cells with an ER inhibitor to induce EMT, followed by the knockdown of ESRP1, which further promoted the EMT process and enhanced the cells' invasive and migratory abilities. This study demonstrates that ESRP1 is a potential breast cancer prognostic marker with subtype specificity and its value as a molecular target needs to be accurately assessed in the context of breast cancer subtypes, as ESRP1 function may be highly dependent on the ER background.