title: Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency.
abstract: The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs, causing disseminated tumor cells to enter latency and the cellular signals in the surrounding nonpermissive tissue microenvironment that maintain the latent state. However, relatively little is known about the mechanisms that enable disseminated tumor cells to escape cancer dormancy or tumor latency. We describe here an in vivo model of solitary metastatic latency in the lung parenchyma. The induction of a localized inflammation in the lungs, initiated by lipopolysaccharide treatment, triggers the awakening of these cells, which develop into macroscopic metastases. The escape from latency is dependent on the expression of Zeb1, a key regulator of the epithelial-to-mesenchymal transition (EMT). Furthermore, activation of the EMT program on its own, as orchestrated by Zeb1, is sufficient to incite metastatic outgrowth by causing carcinoma cells to enter stably into a metastasis-initiating cell state. Cancer Res; 76(23); 6778-84. ©2016 AACR.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: De Cock
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Shibue
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
authors.forename: Anushka
authors.initials: A
authors.lastname: Dongre
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Keckesova
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Reinhardt
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts. weinberg@wi.mit.edu.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.|MIT Ludwig Center for Molecular Oncology, Cambridge, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1