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<title lang=en>Envisioning metastasis as a transdifferentiation phenomenon clarifies discordant results on cancer</title>
<creator>Jehanno, Charly</creator>
<creator>Flouriot, Gilles</creator>
<creator>Nicol-Benoît, Floriane</creator>
<creator>Le Page, Yann</creator>
<creator>Le Goff, Pascale</creator>
<creator>Michel, Denis</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<description>International audience</description>
<source>ISSN: 0888-6008</source>
<source>Breast Disease</source>
<publisher>IOS Press</publisher>
<identifier>hal-01367146</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367146</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367146</source>
<source>Breast Disease, IOS Press, 2016, 36, pp.47--59. 〈10.3233/BD-150210〉</source>
<identifier>DOI : 10.3233/BD-150210</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.3233/BD-150210</relation>
<identifier>PUBMED : 27177343</identifier>
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<language>en</language>
<subject>[SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Cancer is generally conceived as a dedifferentiation process in which quiescent post-mitotic differentiated cells acquire stem-like properties and the capacity to proliferate. This view holds for the initial stages of carcinogenesis but is more questionable for advanced stages when the cells can transdifferentiate into the contractile phenotype associated to migration and metastasis. Singularly from this perspective, the hallmark of the most aggressive cancers would correspond to a genuine differentiation status, even if it is different from the original one. This seeming paradox could help reconciling discrepancies in the literature about the pro-or anti-tumoral functions of candidate molecules involved in cancer and whose actual effects depend on the tumoral grade. These ambiguities which are likely to concern a myriad of molecules and pathways, are illustrated here with the selected examples of chromatin epigenetics and myocardin-related transcription factors, using the human MCF10A and MCF7 breast cancer cells. Self-renewing stem like cells are characterized by a loose chromatin with low levels of the H3K9 trimetylation, but high levels of this mark can also appear in cancer cells acquiring a contractile-type differentiation state associated to metastasis. Similarly, the myocardin-related transcription factor MRTF-A is involved in metastasis and epithelial-mesenchymal transition, whereas this factor is naturally enriched in the quiescent cells which are precisely the most resistant to cancer: cardiomyocytes. These seeming paradoxes reflect the bistable epigenetic landscape of cancer in which dedifferentiated self-renewing and differentiated migrating states are incompatible at the single cell level, though coexisting at the population level. © 2016-IOS Press and the authors. All rights reserved.</description>
<date>2016</date>
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