Myosin II isoform switching mediates invasiveness after TGF-β-induced epithelial-mesenchymal transition

Jordan R. Beach, George S. Hussey, Tyler E. Miller, Arindam Chaudhury, Purvi Patel, James Monslow, Qiao Zheng, Ruth A. Keri, Ofer Reizes, Anne R. Bresnick, Philip H. Howe, Thomas T. Egelhoff

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Abstract

Despite functional significance of nonmuscle myosin II in cell migration and invasion, its role in epithelial-mesenchymal transition (EMT) or TGF-β signaling is unknown. Analysis of normal mammary gland expression revealed that myosin IIC is expressed in luminal cells,whereas myosin IIB expression is up-regulated inmyoepithelial cells that have more mesenchymal characteristics. Furthermore, TGF-β induction of EMT in nontransformed murine mammary gland epithelial cells results in an isoform switch from myosin IIC to myosin IIB and increased phosphorylation of myosin heavy chain (MHC) IIA on target sites known to regulate filament dynamics (S1916, S1943). These expression and phosphorylation changes are downstream of heterogeneous nuclear ribonucleoprotein-E1 (E1), an effector of TGF-β signaling. E1 knockdown drives cells into a migratory, invasive mesenchymal state and concomitantly up-regulates MHC IIB expression and MHC IIA phosphorylation. Abrogation of myosin IIB expression in the E1 knockdown cells has no effect on 2D migration but significantly reduced transmigration and macrophage-stimulated collagen invasion. These studies indicate that transition between myosin IIC/myosin IIB expression is a critical feature of EMT that contributes to increases in invasive behavior.

Original languageEnglish (US)
Pages (from-to)17991-17996
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number44
DOIs
StatePublished - Nov 1 2011

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Beach, J. R., Hussey, G. S., Miller, T. E., Chaudhury, A., Patel, P., Monslow, J., Zheng, Q., Keri, R. A., Reizes, O., Bresnick, A. R., Howe, P. H., & Egelhoff, T. T. (2011). Myosin II isoform switching mediates invasiveness after TGF-β-induced epithelial-mesenchymal transition. Proceedings of the National Academy of Sciences of the United States of America, 108(44), 17991-17996. https://doi.org/10.1073/pnas.1106499108