CD24 interacts with EDN1 to activate NFκB signaling driving triple-negative breast cancer tumor progression and paclitaxel resistance.

Abstract

Breast cancer (BC) is the most common malignant tumor among women worldwide, and its chemotherapy resistance poses a major challenge in clinical treatment. Triple-negative breast cancer (TNBC) is a specific type of breast cancer that has attracted significant attention due to its extremely poor prognosis. The effectiveness of treatment and the prognosis for survival are significantly impacted by paclitaxel (PTX) resistance, a key chemotherapy medication for BC patients, particularly those with TNBC. CD24 is considerably overexpressed in PTX-resistant MDA-MB-231 cells and tissues, and it is directly linked to a bad prognosis for patients, according to this study's bioinformatics analysis and experimental confirmation. According to mechanistic research, CD24 suppresses MDA-MB-231 cell apoptosis while increasing invasion and proliferation by directly interacting with Endothelin-1 (EDN1) to activate the NFκB signaling pathway. Experiments both in vitro and in vivo demonstrate that CD24 knockdown dramatically reduces tumor development and increases PTX sensitivity. The CD24-EDN1-NFκB axis has a crucial role in PTX resistance in TNBC, according to this study, offering a new therapeutic target for treating chemotherapy resistance.