Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
Cholesterol-Mediated Metabolic-mechanotransductive Crosstalk Orchestrates Castration Resistance in Prostate Cancer.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Shaojie, Xu Chao, Jiang Jun, He Limin, Zhou Yike, Li Zhengxuan, Li Yu, Zhang Keying, Yang Fa, Lu Tong, Song Hongtao, Zhu Hai, Hu Zhihao, Zhao Xiaolong, Gan Kai, Li Hongji, Yang Bo, Zhang Rui, Wen Weihong, Han Donghui, Qin Weijun
Аннотация
Biophysical microenvironment fuels therapeutic resistance, yet the contribution of matrix stiffness to castration-resistant prostate cancer (CRPC) remains poorly understood. In this study, we established a metabolic-mechanotransductive crosstalk wherein cholesterol-driven stromal reprogramming amplifies CRPC progression. Mechanistically, full androgen deprivation (FAD) induces cholesterol metabolic rewiring in prostate cancer (PCa) cells that orchestrates the CH25H-dependent phenotype transformation of cancer-associated fibroblast (CAF) into myofibroblastic CAF (myCAF). In turn, the resulting matrix stiffness induces unfolded protein response (UPR) and potentiates IRE1α kinase activity for Xbp1 splicing, while concurrently activating the integrin αVβ3/FAK/STAT3 axis to transcriptionally replenish Xbp1 substrate in PCa cells. This mechanosensitive adaptation thereby confers PCa with resistance to apoptosis induced by FAD. Consequently, pharmacological disruption of this metabolic-mechanotransductive axis by targeting cholesterol metabolism or blockade of IRE1α-XBP1s signaling significantly suppress tumor growth, representing a promising therapeutic strategy for CRPC progression.