{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(9)"],"submitter":["Gattelli A"],"pubmed_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."],"journal":["EMBO molecular medicine"],"pagination":["1335-50"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3799490"],"repository":["biostudies-literature"],"pubmed_title":["Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells."],"pmcid":["PMC3799490"],"pubmed_authors":["Lienhard S","Kenner L","Torres-Arzayus MI","Hynes NE","Boulay A","Nalvarte I","Schreiber M","Carragher N","Schlederer M","Gattelli A","Roloff TC","Macleod KK"],"additional_accession":[]},"is_claimable":false,"name":"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.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Sep","modification":"2021-02-20T04:03:04Z","creation":"2019-03-27T01:17:18Z"},"accession":"S-EPMC3799490","cross_references":{"pubmed":["23868506"],"doi":["10.1002/emmm.201302625"]}}