Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells
| Autor: | Sumit K. Dey, Benu Brata Das, Shekhar Saha, Raman K. Singh, Somiranjan Ghosh, Siddhartha S. Jana, Debdatta Halder, Ditipriya Mallick, Indranil Ghosh, Arijit Ghosh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Nonmuscle Myosin Type IIB Carcinogenesis Nonmuscle Myosin Type IIA 030302 biochemistry & molecular biology Articles Cell Biology Biology Actins Cell biology Gene Expression Regulation Neoplastic Mice 03 medical and health sciences Cell Movement Nonmuscle myosin Gene expression Animals Mechanotransduction Myosin-Light-Chain Kinase Molecular Biology Gene Cytoskeleton Cell Proliferation Methylcholanthrene 030304 developmental biology |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e18-12-0790 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|