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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | 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. Meierjohann, S. |
| Description | Country affiliation: Germany Author Affiliation: Leikam C ( Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.); Hufnagel AL ( Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.); Otto C ( Experimental Surgery, Experimental Transplantation Immunology, Clinic of General, Visceral, Vascular and Pediatric Surgery (Surgical Clinic I), University of Wurzburg Hospital, Wurzburg, Germany.); Murphy DJ ( Institute of Cancer Sciences, Beatson Institute for Cancer Research, University of Glasgow, Glasglow, UK.); Mühling B ( Experimental Surgery, Experimental Transplantation Immunology, Clinic of General, Visceral, Vascular and Pediatric Surgery (Surgical Clinic I), University of Wurzburg Hospital, Wurzburg, Germany.); Kneitz S ( Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.); Nanda I ( Institute for Human Genetics, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.); Schmid M ( Institute for Human Genetics, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.); Wagner TU ( Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.); Haferkamp S ( Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.); Bröcker EB ( Department of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany.); Schartl M ( 1] Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany [2] Comprehensive Cancer Center Mainfranken, University Hospital Wurzburg, Wurzburg, Germany.); Meierjohann S ( 1] Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany [2] Comprehensive Cancer Center Mainfranken, University Hospital Wurzburg, Wurzburg, Germany.) |
| 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-RAS(61K) 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. |
| File Format | HTM / HTML |
| e-ISSN | 20414889 |
| DOI | 10.1038/cddis.2015.71 |
| Journal | Cell Death and Disease |
| Volume Number | 6 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2015-04-02 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Amino Acid Sequence Research Support, Non-u.s. Gov't Cell Proliferation Signal Transduction Gtp Phosphohydrolases Nevus Molecular Sequence Data Melanocytes Cell Aging Neoplastic Stem Cells Metabolism Membrane Proteins Discipline Cell Biology Pathology Animals Heterografts Mice, Nude Physiology Mice In Vitro Techniques |
| Content Type | Text |
| Resource Type | Article |
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