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

• Published in: Oncogene Vol. 35; no. 33; pp. 4302 - 4311
• Main Authors: Somarelli, J A, Schaeffer, D, Marengo, M S, Bepler, T, Rouse, D, Ware, K E, Hish, A J, Zhao, Y, Buckley, A F, Epstein, J I, Armstrong, A J, Virshup, D M, Garcia-Blanco, M A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.08.2016; Nature Publishing Group
• Subjects: 13/31; 14/34; 14/35; 14/63; 631/67; 631/80; 64/60; Animals; Apoptosis; Cancer; Cell adhesion & migration; Cell Biology; Cell Proliferation; Epithelial-Mesenchymal Transition; Female; Genotype & phenotype; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Metastasis; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasms - pathology; Oncology; Original; original-article; Plastics
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2015.497

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.