UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance.

ABSTRACT: UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER⁺) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER⁺ breast cancer tissues than in ER-negative (ER^-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER⁺ breast cancer but not in those with ER^- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functio

SUBMITTER: Lin X 

PROVIDER: S-EPMC11322533 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature