ECM (collagen) mediated signaling drives the emergence of androgen independence in prostate cancer cells

细胞外基质(胶原蛋白)介导的信号传导驱动前列腺癌细胞雄激素非依赖性的出现。

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Abstract

Extracellular matrix is a major structural component of the tumor microenvironment. It is a dynamic entity that undergoes continuous deposition, remodeling and degradation to maintain tissue homeostasis. ECM plays crucial roles in providing mechanical support, modulating the microenvironment as well as serves as a reservoir for signaling molecules. Tissue stiffness is primarily determined by the abundance and cross-linking of the ECM components and in turn influences the aggressiveness and drug-response of the tumors. Collagens make up a large proportion of the total ECM. These collagens, by their interaction with cell-surface molecules like integrins, can also initiate intracellular signaling cascades and influence gene expression and tumor cell behaviour. Our group has previously identified eight different collagen types to be overexpressed in prostate cancer tissues or cultured cancer-associated fibroblasts. In this study, we have investigated•The effect of collagen on prostate cancer cell proliferation, migration and chemosensitivity•The effect of collagen-initiated signaling on androgen receptor-target gene expression under androgen-deprived conditions The results presented here suggest that under androgen-deprived conditions, ECM-mediated signaling (through FAK) can regulate AR-mediated target genes and cell proliferation. This could be a potential mechanism for emergence of androgen independence in prostate cancer.

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