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

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.

Automated summary

Dysregulation of autophagy in cancer-associated fibroblasts has been shown to contribute to the malignant phenotypes of human tumors. This study investigated the role of CAFs autophagy in prostate cancer. Results demonstrated that CAFs had higher levels of autophagy compared to normal fibroblasts. Furthermore, inhibition of autophagy in CAFs suppressed the proliferation, migration, and invasion capabilities of PCa cells. Silencing of ATG5 in CAFs also inhibited fibroblast autophagy and suppressed malignant phenotypes of PCa cells. These findings suggest that CAFs play a promotive role in PCa through ATG5-dependent autophagy, providing a novel mechanism for PCa progression.