UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer.

ABSTRACT: Bone metastasis is the main site of metastasis and causes the most deaths in patients with prostate cancer (PCa). The mechanism of bone metastasis is complex and not fully clarified. By RNA sequencing and analysing key pathways in bone metastases of PCa, we found that one of the most important characteristics during PCa bone metastasis was G1/S transition acceleration caused by low protein levels of p16INK4a (p16). Interestingly, we demonstrated that UBE2S bound and degraded p16 through K11- rather than K48- or K63-linked ubiquitination, which accelerated PCa tumour cell G1/S transition in vivo and in vitro. Moreover, UBE2S also stabilized β-catenin through K11-linked ubiquitination, leading to enhanced migration and invasion of tumour cells in PCa bone metastasis. Based on o

SUBMITTER: Peng S 

PROVIDER: S-EPMC9134922 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature