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

被引:96
作者
Beach, Jordan R. [1 ,2 ]
Hussey, George S. [4 ]
Miller, Tyler E. [1 ]
Chaudhury, Arindam [5 ]
Patel, Purvi [6 ]
Monslow, James [1 ]
Zheng, Qiao [1 ]
Keri, Ruth A. [3 ]
Reizes, Ofer [1 ]
Bresnick, Anne R. [6 ]
Howe, Philip H. [4 ]
Egelhoff, Thomas T. [1 ]
机构
[1] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44195 USA
[2] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
[4] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA
[5] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA
[6] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA
基金
美国国家卫生研究院;
关键词
HEAVY-CHAIN PHOSPHORYLATION; PROTEIN-KINASE-C; NONMUSCLE MYOSIN; GENE-EXPRESSION; SIGNALING PATHWAY; CARCINOMA-CELLS; CANCER CELLS; B GENE; GROWTH; MIGRATION;
D O I
10.1073/pnas.1106499108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Despite functional significance of nonmuscle myosin II in cell migration and invasion, its role in epithelial-mesenchymal transition (EMT) or TGF-beta 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 in myoepithelial cells that have more mesenchymal characteristics. Furthermore, TGF-beta 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-beta 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.
引用
收藏
页码:17991 / 17996
页数:6
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