HES6 enhances the motility of alveolar rhabdomyosarcoma cells

Journal Article · Tue Jan 01 04:00:00 EST 2013 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2012.08.010· OSTI ID:22215476

Wickramasinghe, Caroline M ^[1]; Domaschenz, Renae ^[1]; Amagase, Yoko ^[1]; Williamson, Daniel ^[2]; Missiaglia, Edoardo; Shipley, Janet ^[2]; Murai, Kasumi ^[1]

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1. MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke's Hospital Cambridge, CB2 0XZ (United Kingdom)
2. Molecular Cytogenetics, The Institute of Cancer Research, Sutton SM2 5NG (United Kingdom)

Absract: 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.

• OSTI ID: 22215476
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 319; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
CELL CYCLE
CELL PROLIFERATION
CONNECTIVE TISSUE
GENES
MESSENGER-RNA
MICE
MICROTUBULES
MUSCLES
PATHOGENESIS
PHENOTYPE
RHABDOMYOSARCOMAS
TRANSCRIPTION FACTORS