Cancer-associated fibroblasts promote malignant phenotypes of prostate cancer cells via autophagy

Autor: XuKai Liu, JiZu Tang, LiQiang Peng, HaiBo Nie, YuanGuang Zhang, Pan Liu
Rok vydání: 2023
Předmět:
Zdroj: Apoptosis. 28:881-891
ISSN: 1573-675X
1360-8185
DOI: 10.1007/s10495-023-01828-2
Popis: Dysregulation of autophagy in cancer-associated fibroblasts (CAFs) has been demonstrated to play a role in malignant phenotypes of human tumors. We intended to investigate the function of CAFs autophagy in prostate cancer (PCa). Firstly, CAFs and normal fibroblasts (NFs) were isolated from cancerous and adjacent normal tissues of PCa patients, for the following experimental preparation. In comparison with NFs, CAFs expressed higher levels of the myofibroblast marker ?-smooth muscle actin (?-SMA) and the mesenchymal marker Vimentin. Besides, CAFs possessed a higher autophagic level than NFs. As for malignant phenotypes, PCa cells co-cultured with CAFs-CM showed greater proliferation, migration and invasion capabilities, while these outcomes were obviously abolished by autophagy inhibition with 3-Methyladenine (3-MA). Moreover, silencing of ATG5 in CAFs inhibited fibroblasts autophagic level and suppressed malignant phenotypes of PCa cells, while ATG5 overexpression in NFs exerted opposite effects. Depletion of ATG5 in CAFs inhibited the xenograft tumor growth and lung metastasis of PCa cells. Taken together, our data demonstrated the promotive effect of CAFs on PCa malignant phenotypes through ATG5-dependent autophagy, suggesting a novel mechanism for PCa progression.
Databáze: OpenAIRE
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