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Neelakantan, D.* ; Zhou, H.* ; Oliphant, M.U.J.* ; Zhang, X.* ; Simon, L. ; Henke, D.M.* ; Shaw, C.A.* ; Wu, M.F.* ; Hilsenbeck, S.G.* ; White, L.D.* ; Lewis, M.T.* ; Ford, H.L.*

EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells.

Nat. Commun. 8:15773 (2017)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models. In human breast tumours, the EMT-transcription factors strongly correlate with activated Hedgehog/GLI signalling but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis via non-cell autonomous effects that activate the Hh pathway. Although all Hh inhibitors may act against tumours with canonical Hh/GLI signalling, only GLI inhibitors would act against non-canonical EMT-induced GLI activation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Epithelial-mesenchymal Transition; Hedgehog Signaling Pathway; Stem-cells; Growth; Chemoresistance; Six1; Transcription; Expression; Disease; Kinase
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 15773 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus