title: To differentiate or not--routes towards metastasis.
abstract: Why are many metastases differentiated? Invading and disseminating carcinoma cells can undergo an epithelial-mesenchymal transition (EMT), which is associated with a gain of stem cell-like behaviour. Therefore, EMT has been linked to the cancer stem cell concept. However, it is a matter of debate how subsequent mesenchymal-epithelial transition (MET) fits into the metastatic process and whether a MET is essential. In this Opinion article, I propose two principle types of metastatic progression: phenotypic plasticity involving transient EMT-MET processes and intrinsic genetic alterations keeping cells in an EMT and stemness state. This simplified classification integrates clinically relevant aspects of dormancy, metastatic tropism and therapy resistance, and implies perspectives on treatment strategies against metastasis.
authors.affiliation: Department of General and Visceral Surgery and Comprehensive Cancer Center, University of Freiburg Medical Center, Hugstetter Str. 55, 79106 Freiburg, Germany. thomas.brabletz@uniklinik-freiburg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
mesh_terms: D002454:Cell Differentiation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000473:pathology