SOX10 ablation arrests cell cycle, induces senescence, and suppresses melanomagenesis

Cronin, J.C., Watkins-Chow, D.E., Incao, A., Hasskamp, J.H., Schonewolf, N., Aoude, L.G., Hayward, N.K., Bastian, B.C., Dummer, R., Loftus, S.K. and Pavan, W.J. (2013) SOX10 ablation arrests cell cycle, induces senescence, and suppresses melanomagenesis. Cancer Research, 73 18: 5709-5718. doi:10.1158/0008-5472.CAN-12-4620

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Author Cronin, J.C.
Watkins-Chow, D.E.
Incao, A.
Hasskamp, J.H.
Schonewolf, N.
Aoude, L.G.
Hayward, N.K.
Bastian, B.C.
Dummer, R.
Loftus, S.K.
Pavan, W.J.
Title SOX10 ablation arrests cell cycle, induces senescence, and suppresses melanomagenesis
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
Publication date 2013-09-15
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-12-4620
Open Access Status DOI
Volume 73
Issue 18
Start page 5709
End page 5718
Total pages 10
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Language eng
Subject 1306 Cancer Research
2730 Oncology
Abstract The transcription factor SOX10 is essential for survival and proper differentiation of neural crest cell lineages, where it plays an important role in the generation and maintenance of melanocytes. SOX10 is also highly expressed in melanoma tumors, but a role in disease progression has not been established. Here, we report that melanoma tumor cell lines require wild-type SOX10 expression for proliferation and SOX10 haploinsufficiency reduces melanoma initiation in the metabotropic glutamate receptor 1 (Grm1Tg) transgenic mouse model. Stable SOX10 knockdown in human melanoma cells arrested cell growth, altered cellular morphology, and induced senescence. Melanoma cells with stable loss of SOX10 were arrested in the G1 phase of the cell cycle, with reduced expression of the melanocyte determining factor microphthalmia-associated transcription factor, elevated expression of p21WAF1 and p27KIP2, hypophosphorylated RB, and reduced levels of its binding partner E2F1. As cell-cycle dysregulation is a core event in neoplastic transformation, the role for SOX10 in maintaining cell-cycle control in melanocytes suggests a rational new direction for targeted treatment or prevention of melanoma.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Created: Fri, 04 Apr 2014, 00:10:09 EST by Matthew Lamb on behalf of School of Medicine