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HES6 enhances the motility of alveolar rhabdomyosarcoma cells

Lookup NU author(s): Dr Daniel Williamson

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Abstract

HES6, a member of the hairy-enhancer-of-split family of transcription factors, plays multiple roles in myogenesis. It is a direct target of the myogenic transcription factor MyoD and has been shown to regulate the formation of the myotome in development, myoblast cell cycle exit and the organization of the actin cytoskeleton during terminal differentiation. Here we investigate the expression and function of HES6 in rhabdomyosarcoma, a soft tissue tumor which expresses myogenic genes but fails to differentiate into muscle. We show that HES6 is expressed at high levels in the subset of alveolar rhabdomyosarcomas expressing PAX/FOXO1 fusion genes (ARMSp). Knockdown of HES6 mRNA in the ARMSp cell line RH30 reduces proliferation and cell motility. This phenotype is rescued by expression of mouse Hes6 which is insensitive to HES6 siRNA. Furthermore, expression microarray analysis indicates that the HES6 knockdown is associated with a decrease in the levels of Transgelin, (TAGLN), a regulator of the actin cytoskeleton. Knockdown of TAGLN decreases cell motility, whilst TAGLN overexpression rescues the motility defect resulting from HES6 knockdown. These findings indicate HES6 contributes to the pathogenesis of ARMSp by enhancing both proliferation and cell motility. (C) 2012 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Wickramasinghe CM, Domaschenz R, Amagase Y, Williamson D, Missiaglia E, Shipley J, Murai K, Jones PH

Publication type: Article

Publication status: Published

Journal: Experimental Cell Research

Year: 2013

Volume: 319

Issue: 1

Pages: 103-112

Print publication date: 01/01/2013

ISSN (print): 0014-4827

ISSN (electronic): 1090-2422

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.yexcr.2012.08.010

DOI: 10.1016/j.yexcr.2012.08.010


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Funding

Funder referenceFunder name
MC_U105370181Medical Research Council

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