Abstract
Fe65 is a brain-enriched adaptor protein known for its role in the action of the Aβ amyloid precursor protein in neuronal cells and Alzheimer’s disease, but little is known about its functions in cancer cells. The present study documents for the first time a role of Fe65 in suppressing breast cancer cell migration and invasion. Mechanistic studies suggest that the suppression is mediated through its phosphotyrosine binding domain 1 that mediates the recruitment of Tip60 to cortactin to stimulate its acetylation. The studies identify the Tip60 acetyltransferase as a cytoplasmic drug target for the therapeutic intervention of metastatic breast cancers.
Highlights
Breast cancer is the second leading cause of cancer death among women in the U.S and most of the deaths are caused by metastasis, a complex behavior of cancer cells involving migration, invasion and microenvironment remodeling[1,2]
It was noted that Fe65 was expressed at high levels in the cytoplasm of invasive breast cancer cells such as MDA-MB-231 and MDA-MB-36142, suggesting a possible role of Fe65 in controlling breast cancer invasion
To further validate the role of HDAC6 in the Fe65 action, we investigated the effect of Fe65 knockdown on cell motility in wild type (WT) and HDAC6 null (HDAC6 KO) mouse embryonic fibroblasts (MEFs)
Summary
Breast cancer is the second leading cause of cancer death among women in the U.S and most of the deaths are caused by metastasis, a complex behavior of cancer cells involving migration, invasion and microenvironment remodeling[1,2]. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate post-translational modifications by adding or removing acetyl-groups from lysine residues of histone and non-histone proteins[4,5,6]. They regulate essentially all cellular processes including cell motility and invasion. The present studies report for the first time a role of Fe65 in suppressing breast cancer migration and invasion by showing that Fe65 binds to cortactin in ERα negative breast cancer cells and promotes its acetylation through the Tip[60] acetyltransferase
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
