Distinct routes to metastasis: Plasticity-dependent and plasticity-independent pathways

J. A. Somarelli; D. Schaeffer; M. S. Marengo; T. Bepler; D. Rouse; K. E. Ware; A. J. Hish; Y. Zhao; A. F. Buckley; J. I. Epstein; A. J. Armstrong; D. M. Virshup; M. A. Garcia-Blanco

doi:10.1038/onc.2015.497

Distinct routes to metastasis: Plasticity-dependent and plasticity-independent pathways

J. A. Somarelli, D. Schaeffer, M. S. Marengo, T. Bepler, D. Rouse, K. E. Ware, A. J. Hish, Y. Zhao, A. F. Buckley, J. I. Epstein, A. J. Armstrong, D. M. Virshup, M. A. Garcia-Blanco

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.

Original language	English (US)
Pages (from-to)	4302-4311
Number of pages	10
Journal	Oncogene
Volume	35
Issue number	33
DOIs	https://doi.org/10.1038/onc.2015.497
State	Published - Aug 18 2016
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/onc.2015.497

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title = "Distinct routes to metastasis: Plasticity-dependent and plasticity-independent pathways",

abstract = "The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.",

author = "Somarelli, {J. A.} and D. Schaeffer and Marengo, {M. S.} and T. Bepler and D. Rouse and Ware, {K. E.} and Hish, {A. J.} and Y. Zhao and Buckley, {A. F.} and Epstein, {J. I.} and Armstrong, {A. J.} and Virshup, {D. M.} and Garcia-Blanco, {M. A.}",

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AU - Somarelli, J. A.

AU - Schaeffer, D.

AU - Marengo, M. S.

AU - Bepler, T.

AU - Rouse, D.

AU - Ware, K. E.

AU - Hish, A. J.

AU - Zhao, Y.

AU - Buckley, A. F.

AU - Epstein, J. I.

AU - Armstrong, A. J.

AU - Virshup, D. M.

AU - Garcia-Blanco, M. A.

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AB - The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.

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Distinct routes to metastasis: Plasticity-dependent and plasticity-independent pathways

Abstract

ASJC Scopus subject areas

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