ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling

BackgroundEarly studies indicated that ASC-J9 (R), an androgen receptor (AR) degradation enhancer, could suppress the prostate cancer (PCa) progression. Here we found ASC-J9 (R) could also suppress the PCa progression via an AR-independent mechanism, which might involve modulating the tumor suppressor ATF3 expression.MethodsThe lentiviral system was used to modify gene expression in C4-2, CWR22Rv1 and PC-3 cells. Western blot and Immunohistochemistry were used to detect protein expression. MTT and Transwell assays were used to test the proliferation and invasion ability.ResultsASC-J9 (R) can suppress PCa cell proliferation and invasion in both PCa C4-2 and CWR22Rv1 cells via altering the ATF3 expression. Further mechanistic studies reveal that ASC-J9 (R) can increase the ATF3 expression via decreasing Glutamate-cysteine ligase catalytic (GCLC) subunit expression, which can then lead to decrease the PTK2 expression. Human clinical studies further linked the ATF3 expression to the PCa progression. Preclinical studies using in vivo mouse model also proved ASC-J9 (R) could suppress AR-independent PCa cell invasion, which could be reversed after suppressing ATF3.ConclusionsASC-J9 (R) can function via altering ATF3/PTK2 signaling to suppress the PCa progression in an AR-independent manner.

Automated summary

ASC-J9 (R) can suppress prostate cancer progression via an androgen receptor-independent mechanism by altering ATF3 expression, leading to decreased PTK2 expression. Clinical and preclinical studies support the role of ATF3/PTK2 signaling in PCa progression.