SPOP enhances FADD degradation and decreases the activeness of the NF-κB signaling pathway in prostate cancer: an in vitro study.

Speckle-type POZ protein (SPOP), FAS-associated protein with death domain (FADD), and nuclear transcription factor-κB (NF-κB) have been shown to be associated with the development of prostate cancer (PCa). FADD has been shown to activate the NF-κB pathway to promote tumorigenesis, while SPOP has been shown to enhance the breakdown of FADD and inhibit the function of the NF-κB signaling pathway in non-small cell lung cancer. The existence of this mechanism has not yet been confirmed in PCa. This study aimed to explore the mechanism by which SPOP regulates FADD and the NF-κB signaling pathway in PCa. Western blot was used to detect the presence of SPOP and FADD in both PCa cells and benign prostatic hyperplasia (BPH) cells. The biological behavior of the PC3 cells with altered levels of SPOP was examined using methods such as Cell Counting Kit 8, flow cytometry, and Transwell assay, and the effects of altering SPOP expression levels on the expression of FADD and NF-κB were assessed by western blot. The interaction between SPOP and FADD was detected by immunoprecipitation assay. The SPOP-overexpression PC3 cells were treated with MG132 inhibitor, and the expression of FADD was detected by western blot. A nude mice model of tumor of PCa with SPOP-overexpression was established, growth of the tumor was observed, and pathology of the tumor was diagnosed. Western blot was used to detect the expression of FADD and NF-κB in the tumor tissues. The PCa cells displayed decreased SPOP expression and increased FADD expression compared to the BPH cells (P<0.05). Additionally, the SPOP-silencing PC3 cells had higher levels of FADD and NF-κB expression than the SPOP-overexpression cells (P<0.05). Proliferation, migration, and invasion activities were lower in the SPOP-overexpression PC3 cells than the SPOP-silencing PC3 cells (P<0.05), and the apoptosis rate was higher in the SPOP-overexpression PC3 cells than the SPOP-silencing PC3 cells (P<0.05). There was an interaction between FADD and SPOP in the PC3 cells. After treatment with MG132, the expression of FADD rebounded compared with that before the treatment in the SPOP-overexpression PC3 cells (P<0.05). The volume and weight of the SPOP-overexpression PC3 tumors in the animal models were smaller than those of the control group (P<0.05). The pathological diagnosis revealed that the SPOP-overexpression tumors had more necrosis, and the expression of FADD and NF-κB in the PCa tumors was reduced when SPOP was overexpressed (P<0.05). There may be a SPOP-FADD-NF-κB regulatory axis in PCa. SPOP facilitates the degradation of FADD, leading to a decrease in the activity of the NF-κB signaling pathway.