Ding J, Kuang P

Estrogen receptor ? (ER?) is the major driver for breast tumor carcinogenesis and progression, while ER? positive breast cancer is the major subtype in breast malignancies, which account for 70% breast cancers in patients. The success of endocrine therapy such as tamoxifen is one of the biggest breakthroughs in breast ...

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cancer treatments. However, the endocrine therapy resistance is a headache problem in breast cancer. Further mechanisms need to be identified to the effect of ER? signaling in controlling breast cancer progression and drug resistance. HOIL-1 was firstly identified as the ER? transcriptional co-activator in modulating estrogen signaling in breast cancer. In our current study, we showed that HOIL-1, which was elevated in breast cancer, related to good prognosis in ER? positive breast cancer, but correlated with poor outcome in endocrine-treated patients. HOIL-1 was required for ER? positive breast cancer proliferation and clone formation, which effect could be rescued by further ER? overexpression. Further mechanism studies showed that HOIL-1 is required for ER? signaling activity in breast cancer cells. HOIL-1 could interact with ER? in the cytosol and modulate ER? stability via inhibiting ER? K48-linked poly-ubiquitination. Thus, our study demonstrated a novel post-translational modification in ER? signaling, which could provide novel strategy for ER?-driven breast cancer therapy.

Date: Jun. 08, 2021

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