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

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. Oncogene advance online publication, 11 January 2016; doi:10. 1038/onc. 2015. 497.

Oncogene. 2016 Jan 11 [Epub ahead of print]

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

Center for RNA Biology, Duke University Medical Center, Durham, NC, USA. , Center for RNA Biology, Duke University Medical Center, Durham, NC, USA. , Center for RNA Biology, Duke University Medical Center, Durham, NC, USA. , Center for RNA Biology, Duke University Medical Center, Durham, NC, USA. , Department of Laboratory Animal Resources, Duke University Medical Center, Durham, NC, USA. , Center for RNA Biology, Duke University Medical Center, Durham, NC, USA. , Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. , Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA. , Department of Pathology, Duke University Medical Center, Durham, NC, USA. , Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA. , Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. , Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore. , Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.

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