Type

Journal Article

Authors

Lorraine O'Driscoll
Richard K Porter
John Crown
Vanesa G Martinez

Subjects

Biochemistry

Topics
cancer cells drug resistant cells flow cytometry stem cell epithelial mesenchymal transition her2 positive breast cancer cancer cell

Neuromedin U alters bioenergetics and expands the cancer stem cell phenotype in HER2-positive breast cancer. (2016)

Abstract Neuromedin U (NmU) is a neuropeptide belonging to the neuromedin family. Recently, we reported a significant association between NmU and breast cancer, particularly correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients, although the mechanism through which it exerts this effect remained unexplained. Investigating this, here we found that ectopic over-expression of NmU in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity. Similar results were observed in HER2-targeted drug-resistant cell variants, which we had previously shown to display increased levels of NmU. Overexpression of NmU also resulted in upregulation of epithelial-mesenchymal transition markers and increased IL-6 secretion which, together with aberrant metabolism, have all been associated with the cancer stem cell (CSC) phenotype. Flow cytometry experiments confirmed that NmU-overexpressing and HER2-targeted drug-resistant cells showed an increased proportion of cells with CSC phenotype (CD44(+) /CD24(-) ). Taken together, our results report a new mechanism of action for NmU in HER2-overexpressing breast cancer that enhances resistance to HER2-targeted drugs through conferring CSC characteristics and expansion of the CSC phenotype.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Lorraine O'Driscoll, Richard K Porter, John Crown, Vanesa G Martinez

Experts in our system

1
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 164
 
2
Richard K Porter
Trinity College Dublin
Total Publications: 52
 
3
John Crown
Dublin City University
Total Publications: 104
 
4
Vanesa G Martinez
Trinity College Dublin
Total Publications: 8