Role of PICK1 in prostate cancer: Modulating epithelial-mesenchymal transition and immune escape through activation of UNC5A.

BACKGROUND: Unc-5 netrin receptor A (UNC5A) activated by protein interacting with C kinase 1 (PICK1) serves as therapeutic target to mitigate the malignant development of prostate cancer (PC). Herein, the mechanism of PICK1/UNC5A axis in PC disease is further investigated. METHODS: Cell functional tests (CCK-8 and Transwell assay) were performed in PC3 and 22Rv1 prostate cancer cell lines to examine how UNC5A/PICK1 overexpression and short hairpin RNA against UNC5A (shUNC5A)/shPICK1 affect PC cell biological functions. Using qRT-PCR and western blot, UNC5A and epithelial-mesenchymal transition (EMT)-related genes and proteins (matrix metallopeptidase 2 (MMP2), MMP9, E-cadherin, and N-cadherin) were measured. How PICK1/UNC5A axis regulates PC cell biology was determined via rescue test. Natural killer (NK) cells were co-cultured with prostate cancer cells, and the effect of PICK1/UNC5A on immune escape of PC was detected by cytotoxicity test, colony formation test and scratch method. RESULTS: UNC5A was lowly expressed in PC cells, with relatively higher expression in PC3 cells and lower expression in 22Rv1 cells. In both cell lines, migration, invasion and EMT of PC cells were promoted by shUNC5A/shPICK1 yet inhibited by overexpressed UNC5A/PICK1. PICK1 could activate UNC5A expression, while suppressing the migration, invasion, EMT and immune escape of PC cells. Moreover, the effects of shUNC5A and shPICK1 were reversed by PICK1 and UNC5A overexpression, respectively, and the converse was also true. CONCLUSIONS: PICK1 hampers the EMT and immune escape of PC cells by activating UNC5A.