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Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells

Though many cancers are known to show up-regulation of nonmuscle myosin (NM) IIA and IIB, the mechanism by which NMIIs aid in cancer development remains unexplored. Here we demonstrate that tumor-generating, fibroblast-like cells isolated from 3-methylcholanthrene (3MC)-induced murine tumor exhibit...

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Autores principales: Halder, Debdatta, Saha, Shekhar, Singh, Raman K., Ghosh, Indranil, Mallick, Ditipriya, Dey, Sumit K., Ghosh, Arijit, Das, Benu Brata, Ghosh, Somiranjan, Jana, Siddhartha S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724700/
https://www.ncbi.nlm.nih.gov/pubmed/30995168
http://dx.doi.org/10.1091/mbc.E18-12-0790
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author Halder, Debdatta
Saha, Shekhar
Singh, Raman K.
Ghosh, Indranil
Mallick, Ditipriya
Dey, Sumit K.
Ghosh, Arijit
Das, Benu Brata
Ghosh, Somiranjan
Jana, Siddhartha S.
author_facet Halder, Debdatta
Saha, Shekhar
Singh, Raman K.
Ghosh, Indranil
Mallick, Ditipriya
Dey, Sumit K.
Ghosh, Arijit
Das, Benu Brata
Ghosh, Somiranjan
Jana, Siddhartha S.
author_sort Halder, Debdatta
collection PubMed
description Though many cancers are known to show up-regulation of nonmuscle myosin (NM) IIA and IIB, the mechanism by which NMIIs aid in cancer development remains unexplored. Here we demonstrate that tumor-generating, fibroblast-like cells isolated from 3-methylcholanthrene (3MC)-induced murine tumor exhibit distinct phospho-dependent localization of NMIIA and NMIIB at the perinuclear area and tip of the filopodia and affect cell migration differentially. While NMIIA-KD affects protrusion dynamics and increases cell directionality, NMIIB-KD lowers migration speed and increases filopodial branching. Strategically located NMIIs at the perinuclear area colocalize with the linker of nucleoskeleton and cytoskeleton (LINC) protein Nesprin2 and maintain the integrity of the nuclear-actin cap. Interestingly, knockdown of NMIIs results in altered expression of genes involved in epithelial-to-mesenchymal transition, angiogenesis, and cellular senescence. NMIIB-KD cells display down-regulation of Gsc and Serpinb2, which is strikingly similar to Nesprin2-KD cells as assessed by quantitative PCR analysis. Further gene network analysis predicts that NMIIA and NMIIB may act on similar pathways but through different regulators. Concomitantly, knockdown of NMIIA or NMIIB lowers the growth rate and tumor volume of 3MC-induced tumor in vivo. Altogether, these results open a new window to further investigate the effect of LINC-associated perinuclear actomyosin complex on mechanoresponsive gene expression in the growing tumor.
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spelling pubmed-67247002019-09-06 Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells Halder, Debdatta Saha, Shekhar Singh, Raman K. Ghosh, Indranil Mallick, Ditipriya Dey, Sumit K. Ghosh, Arijit Das, Benu Brata Ghosh, Somiranjan Jana, Siddhartha S. Mol Biol Cell Articles Though many cancers are known to show up-regulation of nonmuscle myosin (NM) IIA and IIB, the mechanism by which NMIIs aid in cancer development remains unexplored. Here we demonstrate that tumor-generating, fibroblast-like cells isolated from 3-methylcholanthrene (3MC)-induced murine tumor exhibit distinct phospho-dependent localization of NMIIA and NMIIB at the perinuclear area and tip of the filopodia and affect cell migration differentially. While NMIIA-KD affects protrusion dynamics and increases cell directionality, NMIIB-KD lowers migration speed and increases filopodial branching. Strategically located NMIIs at the perinuclear area colocalize with the linker of nucleoskeleton and cytoskeleton (LINC) protein Nesprin2 and maintain the integrity of the nuclear-actin cap. Interestingly, knockdown of NMIIs results in altered expression of genes involved in epithelial-to-mesenchymal transition, angiogenesis, and cellular senescence. NMIIB-KD cells display down-regulation of Gsc and Serpinb2, which is strikingly similar to Nesprin2-KD cells as assessed by quantitative PCR analysis. Further gene network analysis predicts that NMIIA and NMIIB may act on similar pathways but through different regulators. Concomitantly, knockdown of NMIIA or NMIIB lowers the growth rate and tumor volume of 3MC-induced tumor in vivo. Altogether, these results open a new window to further investigate the effect of LINC-associated perinuclear actomyosin complex on mechanoresponsive gene expression in the growing tumor. The American Society for Cell Biology 2019-06-01 /pmc/articles/PMC6724700/ /pubmed/30995168 http://dx.doi.org/10.1091/mbc.E18-12-0790 Text en © 2019 Halder et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Halder, Debdatta
Saha, Shekhar
Singh, Raman K.
Ghosh, Indranil
Mallick, Ditipriya
Dey, Sumit K.
Ghosh, Arijit
Das, Benu Brata
Ghosh, Somiranjan
Jana, Siddhartha S.
Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
title Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
title_full Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
title_fullStr Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
title_full_unstemmed Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
title_short Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
title_sort nonmuscle myosin iia and iib differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724700/
https://www.ncbi.nlm.nih.gov/pubmed/30995168
http://dx.doi.org/10.1091/mbc.E18-12-0790
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