Activating transcription factor 6 promotes proliferation, migration and invasion of PC3 human prostate cancer cells through Hippo-YAP signaling pathway

Objective To investigate the effects of activating transcription factor 6 (ATF6) on the proliferation, migration and invasion of prostate cancer PC3 cells. Methods Prostate cancer tissue samples and benign prostatic hyperplasia tissue samples were collected, then the mRNA and protein levels of ATF6 were detected by qRT-PCR and Western blotting, respectively. Lentivirus with ATF6 shRNA was transfected into PC3 cells to downregulate ATF6 expression, then CCK8 and EdU assays were adopted to determine the proliferation of PC3 cells, and wound-healing and Transwell invasion tests were performed to evaluate the migration and invasion abilities of PC3 cells. Nude mouse xenograft models were used to assess the influence of ATF6 on tumorigenesis in vivo. Moreover, the association between Yes-associated protein (YAP) and ATF6 was analyzed using online JASPAR database prediction and luciferase reporter. The mRNA and protein levels of YAP were detected with qRT-PCR and immunofluorescence assay, and the mRNA levels of 2 downstream factors of YAP, connective tissue growth factor (CTGF) and cysteine-rich 61 (Cyr61), were also measured by qRT-PCR. Results The mRNA and protein levels of ATF6 in prostate cancer tissues were significantly increased (P < 0.05). Knockdown of ATF6 decreased the proliferation, invasion, and migration abilities of PC3 cells (P < 0.05), and the in vivo study showed that ATF6-knockdown attenuated tumor growth as well (P < 0.05). JASPAR database predicted that there was an initiation binding site between ATF6 and YAP, and the luciferase reporter assay also confirmed the interaction between them. In addition, YAP expression was remarkably downregulated after knockdown of ATF6 (P < 0.05), and the mRNA level of YAP downstream genes CTGF and Cyr61 were also decreased accordingly (P < 0.05). Conclusion ATF6 promotes the proliferation, migration, and invasion of prostate cancer PC3 cells through Hippo-YAP signaling pathway.