Leikam, C. et al. (2015) In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells. Cell Death and Disease, 6(4), e1711. (doi: 10.1038/cddis.2015.71) (PMID:25837487)
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Abstract
Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Murphy, Professor Daniel |
Authors: | Leikam, C., Hufnagel, A.L., Otto, C., Murphy, D.J., Mühling, B., Kneitz, S., Nanda, I., Schmid, M., Wagner, T.U., Haferkamp, S., Bröcker, E.-B., Schartl, M., and Meierjohann, S. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Cell Death and Disease |
Publisher: | Nature Publishing Group |
ISSN: | 2041-4889 |
ISSN (Online): | 2041-4889 |
Copyright Holders: | Copyright © 2015 The Authors |
First Published: | First published in Cell Death and Disease 6(4):e1711 |
Publisher Policy: | Reproduced under a Creative Commons License |
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