Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
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Author
Gattelli, Albana
Nalvarte, Ivan
Boulay, Anne
Roloff, Tim C
Schreiber, Martin
Carragher, Neil
Macleod, Kenneth K
Schlederer, Michaela
Lienhard, Susanne
Kenner, Lukas
Hynes, Nancy E
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1002/emmm.201302625Metadata
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Gattelli, A., I. Nalvarte, A. Boulay, T. C. Roloff, M. Schreiber, N. Carragher, K. K. Macleod, et al. 2013. “Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells.” EMBO Molecular Medicine 5 (9): 1335-1350. doi:10.1002/emmm.201302625. http://dx.doi.org/10.1002/emmm.201302625.Abstract
We show that elevated levels of Ret receptor are found in different sub-types of human breast cancers and that high Ret correlates with decreased metastasis-free survival. The role of Ret in ER+ breast cancer models was explored combining in vitro and in vivo approaches. Our analyses revealed that ligand-induced Ret activation: (i) stimulates migration of breast cancer cells; (ii) rescues cells from anti-proliferative effects of endocrine treatment and (iii) stimulates expression of cytokines in the presence of endocrine agents. Indeed, we uncovered a positive feed-forward loop between the inflammatory cytokine IL6 and Ret that links them at the expression and the functional level. In vivo inhibition of Ret in a metastatic breast cancer model inhibits tumour outgrowth and metastatic potential. Ret inhibition blocks the feed-forward loop by down-regulating Ret levels, as well as decreasing activity of Fak, an integrator of IL6-Ret signalling. Our results suggest that Ret kinase should be considered as a novel therapeutic target in subsets of breast cancer.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799490/pdf/Terms of Use
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