Dataset Information

MYH9: Structure, functions and role of non-muscle myosin IIA in human disease.

ABSTRACT: The MYH9 gene encodes the heavy chain of non-muscle myosin IIA, a widely expressed cytoplasmic myosin that participates in a variety of processes requiring the generation of intracellular chemomechanical force and translocation of the actin cytoskeleton. Non-muscle myosin IIA functions are regulated by phosphorylation of its 20?kDa light chain, of the heavy chain, and by interactions with other proteins. Variants of MYH9 cause an autosomal-dominant disorder, termed MYH9-related disease, and may be involved in other conditions, such as chronic kidney disease, non-syndromic deafness, and cancer. This review discusses the structure of the MYH9 gene and its protein, as well as the regulation and physiologic functions of non-muscle myosin IIA with particular reference to embryonic development. Moreover, the review focuses on current knowledge about the role of MYH9 variants in human disease.

SUBMITTER: Pecci A

PROVIDER: S-EPMC5970098 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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MYH9: Structure, functions and role of non-muscle myosin IIA in human disease.

Pecci Alessandro A Ma Xuefei X Savoia Anna A Adelstein Robert S RS

Gene 20180419

The MYH9 gene encodes the heavy chain of non-muscle myosin IIA, a widely expressed cytoplasmic myosin that participates in a variety of processes requiring the generation of intracellular chemomechanical force and translocation of the actin cytoskeleton. Non-muscle myosin IIA functions are regulated by phosphorylation of its 20 kDa light chain, of the heavy chain, and by interactions with other proteins. Variants of MYH9 cause an autosomal-dominant disorder, termed MYH9-related disease, and may ...[more]

PMID: 29679756

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Project description:BackgroundGlioblastoma (GBM) is the most aggressive form of brain tumor and has vascular-rich features. The S100A4/non-muscle myosin IIA (NMIIA) axis contributes to aggressive phenotypes in a variety of human malignancies, but little is known about its involvement in GBM tumorigenesis. Herein, we examined the role of the S100A4/NMIIA axis during tumor progression and vasculogenesis in GBM.MethodsWe performed immunohistochemistry for S100A4, NMIIA, and two hypoxic markers, hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9), in samples from 94 GBM cases. The functional impact of S100A4 knockdown and hypoxia were also assessed using a GBM cell line.ResultsIn clinical GBM samples, overexpression of S100A4 and NMIIA was observed in both non-pseudopalisading (Ps) and Ps (-associated) perinecrotic lesions, consistent with stabilization of HIF-1α and CA9. CD34(+) microvascular densities (MVDs) and the interaction of S100A4 and NMIIA were significantly higher in non-Ps perinecrotic lesions compared to those in Ps perinecrotic areas. In non-Ps perinecrotic lesions, S100A4(+)/HIF-1α(-) GBM cells were recruited to the surface of preexisting host vessels in the vascular-rich areas. Elevated vascular endothelial growth factor A (VEGFA) mRNA expression was found in S100A4(+)/HIF-1α(+) GBM cells adjacent to the vascular-rich areas. In addition, GBM patients with high S100A4 protein expression had significantly worse OS and PFS than did patients with low S100A4 expression. Knockdown of S100A4 in the GBM cell line KS-1 decreased migration capability, concomitant with decreased Slug expression; the opposite effects were elicited by blebbistatin-dependent inhibition of NMIIA.ConclusionS100A4(+)/HIF-1α(-) GBM cells are recruited to (and migrate along) preexisting vessels through inhibition of NMIIA activity. This is likely stimulated by extracellular VEGF that is released by S100A4(+)/HIF-1α(+) tumor cells in non-Ps perinecrotic lesions. In turn, these events engender tumor progression via acceleration of pro-tumorigenic vascular functions. Video abstract.

Dataset Information

MYH9: Structure, functions and role of non-muscle myosin IIA in human disease.

Publications

MYH9: Structure, functions and role of non-muscle myosin IIA in human disease.

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