Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3443
Keywords
-
Categories
Funding
- Takeda Science Foundation
- Naito Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Takamatsunomiya Princess Memorial Foundation
- Project Future of Relay For Life Japan
- MEXT [23134504, 25134712]
- Grants-in-Aid for Scientific Research [24109017, 25430186, 23134504] Funding Source: KAKEN
Ask authors/readers for more resources
The acquisition of endocrine resistance is a common obstacle in endocrine therapy of patients with oestrogen receptor-alpha (ER alpha)-positive breast tumours. We previously demonstrated that the BIG3-PHB2 complex has a crucial role in the modulation of oestrogen/ER alpha signalling in breast cancer cells. Here we report a cell-permeable peptide inhibitor, called ERAP, that regulates multiple ERa-signalling pathways associated with tamoxifen resistance in breast cancer cells by inhibiting the interaction between BIG3 and PHB2. Intrinsic PHB2 released from BIG3 by ERAP directly binds to both nuclear-and membrane-associated ER alpha, which leads to the inhibition of multiple ER alpha-signalling pathways, including genomic and non-genomic ERa activation and ER alpha phosphorylation, and the growth of ER alpha-positive breast cancer cells both in vitro and in vivo. More importantly, ERAP treatment suppresses tamoxifen resistance and enhances tamoxifen responsiveness in ER alpha-positive breast cancer cells. These findings suggest inhibiting the interaction between BIG3 and PHB2 may be a new therapeutic strategy for the treatment of luminal-type breast cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available