Regulation of Cancer Stem Cell-like Properties by Deubiquitinating enzymes UCH-L1 and UCH-L3 in Prostate Cancer Cells

초록

The advanced and metastatic form of prostate cancer, castration-resistant prostate cancer (CRPC), is currently incurable. The relapse and chemotherapy resistant property of CRPC is contributed to prostate cancer stem cells (CSCs). It is urgent to understand the regulatory mechanism of stem cell-like behavior to overcome the lethal prostate cancer. However, the regulation factors of prostate CSCs properties are not extensively studied. Here we found that UCH-L1 and UCH-L3 differentially regulated the cancer stem cell-like properties of prostate cancer cells. Knockdown of UCH-L3 or ectopic expression of UCH-L1 increased the CSC markers of pluripotency including Oct4, Nanog, and Bmi1 in message and protein level. UCH-L3 knockdown increased the sphere formation and showed chemoresistance toward doxorubicin, etoposide, and MTX. Sphere formation and chemoresistant effect of UCH-L1 overexpressed cell line were similar to UCH-L3 knockdown cell line. Our findings strongly suggest that UCH-L1 and UCH-L3 are novel regulators of prostate cancer stem-cell like properties and shed lights on innovative therapeutic target for the treatment of refractory and metastatic prostate cancers.