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

MedStar author(s):
Citation: Cancer Research. 73(18):5709-18, 2013 Sep 15.PMID: 23913827Institution: MedStar Franklin Square Medical CenterDepartment: Maryland Melanoma CenterForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tSubject headings: *Cell Aging | *Cell Cycle | *Disease Models, Animal | *Melanoma/pa [Pathology] | *Receptors, Metabotropic Glutamate/ph [Physiology] | *SOXE Transcription Factors/ph [Physiology] | Animals | Apoptosis | Blotting, Western | Cell Proliferation | Humans | Immunoenzyme Techniques | Melanoma/ge [Genetics] | Melanoma/pc [Prevention & Control] | Mice | Mice, Transgenic | Phenotype | Real-Time Polymerase Chain Reaction | Reverse Transcriptase Polymerase Chain Reaction | RNA, Messenger/ge [Genetics]Year: 2013Local holdings: Available online through MWHC library: 1941- present, Available in print through MWHC library: 1999 - 2003ISSN:
  • 0008-5472
Name of journal: Cancer researchAbstract: 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 (Grm1(Tg)) 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.Copyright ©2013 AACR.All authors: Aoude LG, Bastian BC, Cronin JC, Dummer R, Hasskamp JH, Hayward NK, Incao A, Loftus SK, Pavan WJ, Schonewolf N, Watkins-Chow DEFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2016-07-15
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 23913827 Available 23913827

Available online through MWHC library: 1941- present, Available in print through MWHC library: 1999 - 2003

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 (Grm1(Tg)) 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.Copyright ©2013 AACR.

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