Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells

DSpace/Manakin Repository

Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells

Citable link to this page

 

 
Title: Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells
Author: Alam, Maroof; Rajabi, Hasan; Ahmad, Rehan; Jin, Caining; Kufe, Donald

Note: Order does not necessarily reflect citation order of authors.

Citation: Alam, Maroof, Hasan Rajabi, Rehan Ahmad, Caining Jin, and Donald Kufe. 2014. “Targeting the MUC1-C oncoprotein inhibits self-renewal capacity of breast cancer cells.” Oncotarget 5 (9): 2622-2634.
Full Text & Related Files:
Abstract: The capacity of breast cancer cells to form mammospheres in non-adherent serum-free culture is used as a functional characteristic of the self-renewing stem-like cell population. The present studies demonstrate that silencing expression of the MUC1-C oncoprotein inhibits growth of luminal MCF-7 and HER2-overexpressing SKBR3 breast cancer cells as mammospheres. We also show that triple-negative MDA-MB-468 breast cancer cells are dependent on MUC1-C for growth as mammospheres and tumor xenografts. Similar results were obtained when MUC1-C function was inhibited by expression of a MUC1-C(CQC→AQA) mutant. Moreover, treatment with the MUC1-C inhibitor GO-203, a cell penetrating peptide that binds to the MUC1-C cytoplasmic domain and blocks MUC1-C function, confirmed the importance of this target for self-renewal. The mechanistic basis for these findings is supported by the demonstration that MUC1-C activates NF-κB, occupies the IL-8 promoter with NF-κB, and induces IL-8 transcription. MUC1-C also induces NF-κB-dependent expression of the IL-8 receptor, CXCR1. In concert with these results, targeting MUC1-C with GO-203 suppresses IL-8/CXCR1 expression and disrupts the formation of established mammospheres. Our findings indicate that MUC1-C contributes to the self-renewal of breast cancer cells by activating the NF-κB→IL-8/CXCR1 pathway and that targeting MUC1-C represents a potential approach for the treatment of this population.
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058032/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406707
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters