Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells

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 l...

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Main Authors:	Gattelli, Albana, Nalvarte, Ivan, Boulay, Anne, Roloff, Tim C, Schreiber, Martin, Carragher, Neil, Macleod, Kenneth K, Schlederer, Michaela, Lienhard, Susanne, Kenner, Lukas, Torres-Arzayus, Maria I, Hynes, Nancy E
Format:	Online
Language:	English
Published:	Blackwell Publishing Ltd 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799490/

id	pubmed-3799490
recordtype	oai_dc
spelling	pubmed-37994902013-10-23 Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells Gattelli, Albana Nalvarte, Ivan Boulay, Anne Roloff, Tim C Schreiber, Martin Carragher, Neil Macleod, Kenneth K Schlederer, Michaela Lienhard, Susanne Kenner, Lukas Torres-Arzayus, Maria I Hynes, Nancy E Research Articles 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. Blackwell Publishing Ltd 2013-09 2013-07-19 /pmc/articles/PMC3799490/ /pubmed/23868506 http://dx.doi.org/10.1002/emmm.201302625 Text en © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gattelli, Albana Nalvarte, Ivan Boulay, Anne Roloff, Tim C Schreiber, Martin Carragher, Neil Macleod, Kenneth K Schlederer, Michaela Lienhard, Susanne Kenner, Lukas Torres-Arzayus, Maria I Hynes, Nancy E
spellingShingle	Gattelli, Albana Nalvarte, Ivan Boulay, Anne Roloff, Tim C Schreiber, Martin Carragher, Neil Macleod, Kenneth K Schlederer, Michaela Lienhard, Susanne Kenner, Lukas Torres-Arzayus, Maria I Hynes, Nancy E Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
author_facet	Gattelli, Albana Nalvarte, Ivan Boulay, Anne Roloff, Tim C Schreiber, Martin Carragher, Neil Macleod, Kenneth K Schlederer, Michaela Lienhard, Susanne Kenner, Lukas Torres-Arzayus, Maria I Hynes, Nancy E
author_sort	Gattelli, Albana
title	Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
title_short	Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
title_full	Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
title_fullStr	Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
title_full_unstemmed	Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
title_sort	ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells
description	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.
publisher	Blackwell Publishing Ltd
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799490/
_version_	1612019103403343872

Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells

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