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.
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Somarelli
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Schaeffer
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Marengo
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bepler
authors.affiliation: Department of Laboratory Animal Resources, Duke University Medical Center, Durham, NC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Rouse
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Ware
authors.affiliation: Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hish
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Buckley
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA.|Department of Urology, Johns Hopkins Hospital, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: J I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Solid Tumor Program and the Duke Prostate Center, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: D M
authors.initials: DM
authors.lastname: Virshup
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, NC, USA.|Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.|Program in Molecular Genetics and Genomics, Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Garcia-Blanco
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology