Extracellular Matrix Stiffness Enhancement Promotes Docetaxel Resistance in Prostate Cancer via Inhibition of Apoptosis Mediated by Upregulation of PRRX1

作者：Jiahao Chen, Mengting Chen, Zhiwen Xie, Luheng Shen, Juntao Jiang, Shujie Xia · 发表于：International Journal of Medical Sciences · 年份：2025 · DOI：10.7150/ijms.111171 · 被引用次数：3 · 研究领域：Cell Adhesion Molecules Research、Hippo pathway signaling and YAP/TAZ、Caveolin-1 and cellular processes

Background: Prostate cancer (PCa) poses a significant health burden for men, with docetaxel constituting the primary therapeutic option for patients with metastatic PCa.However, the mechanisms governing docetaxel resistance remain incompletely understood.Several studies have implicated the role of the extracellular matrix (ECM) stiffness in cancer drug resistance, yet the precise role of ECM stiffness in docetaxel resistance in PCa remains elusive.The aim of this study was to explore the influence of ECM stiffness on docetaxel resistance in PCa and elucidate the underlying molecular mechanisms, thereby providing novel insights into PCa treatment.Methods: Polyacrylamide gels of varying stiffness were utilized to mimic different ECM stiffness conditions.The sensitivity of PCa cells to docetaxel was evaluated using CCK-8, TUNEL staining, flow cytometry, and western blotting.RNA-seq was employed to analyze the transcriptomic effects of different ECM stiffness on PC-3 cells.Western blotting, qPCR, and siRNA were utilized to validate the regulatory role of the key gene in the sensitivity of PCa cells to docetaxel under varying stiffness conditions.Results: Our findings indicate that high ECM stiffness enhances docetaxel resistance in PCa cells by inhibiting docetaxel-induced apoptosis.This process is mediated through the integrin-related mechanotransduction pathway.Specifically, high ECM stiffness upregulates the expression of PRRX1, thereby promoting docetaxel resistance in PCa ce...