Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis

被引:14
作者
Toro, Laura E. Norwood [1 ]
Wang, Yarong [2 ]
Condeelis, John S. [2 ,6 ,7 ]
Jones, Joan G. [2 ,4 ,5 ,6 ]
Backer, Jonathan M. [1 ,3 ]
Bresnick, Anne R. [1 ]
机构
[1] Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dept Anat & Struct Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Dept Mol Pharmacol, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[4] Albert Einstein Coll Med, Dept Pathol, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[5] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[6] Albert Einstein Coll Med, Integrated Imaging Program, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[7] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, 1300 Morris Pk Ave, Bronx, NY 10461 USA
关键词
Myosin-II; Phosphorylation; Invasion; Matrix degradation; Invadopodia; BREAST-CANCER; MATRIX DEGRADATION; CELL INVASION; PODOSOME DYNAMICS; CARCINOMA-CELLS; IN-VIVO; INVADOPODIA; MATURATION; S100A4; MATRIX-METALLOPROTEINASE-9;
D O I
10.1016/j.yexcr.2018.06.028
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Nonmuscle myosin-IIA (NMHC-IIA) heavy chain phosphorylation has gained recognition as an important feature of myosin-II regulation. In previous work, we showed that phosphorylation on 51943 promotes myosin-IIA filament disassembly in vitro and enhances EGF-stimulated lamellipod extension of breast tumor cells. However, the contribution of NMHC-IIA 51943 phosphorylation to the modulation of invasive cellular behavior and metastasis has not been examined. Stable expression of phosphomimetic (S1943E) or non-phosphorylatable (S1943A) NMHC-IIA in breast cancer cells revealed that 51943 phosphorylation enhances invadopodia function, and is critical for matrix degradation in vitro and experimental metastasis in vivo. These studies demonstrate a novel link between NMHC-IIA 51943 phosphorylation, the regulation of extracellular matrix degradation and tumor cell invasion and metastasis.
引用
收藏
页码:273 / 282
页数:10
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