Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis

Abstract

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 S1943 promotes myosin-IIA filament disassembly in vitro and enhances EGF-stimulated lamellipod extension of breast tumor cells. However, the contribution of NMHC-IIA S1943 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 S1943 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 S1943 phosphorylation, the regulation of extracellular matrix degradation and tumor cell invasion and metastasis.

HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

“…S3A and S3B ). The prediction of Group-based Prediction System, Version 2.0 (GPS 2.0; http://gps.biocuckoo.org/ ) showed that the fragment of EATR contained two phosphorylation sites, S1916 and S1943, which were reported to regulate the assembly of myosin-IIA filaments 24 , 37 . To identify the HBXIP-promoted phosphorylation sites of EATR, the S1916 and S1943 sites were mutated to alanine (A, mimics of phosphorylation deficiency).…”

A novel mechanoeffector role of fibroblast S100A4 in myofibroblast transdifferentiation and fibrosis

“…WT and S100A4 KO MLFs were plated onto fibronectin-coated glass coverslip-bottom dishes and transfected with the EGFP NMII-A fusion protein expressing plasmid, pEGFP-C3-NMHC-IIA (kindly provided by Dr Anne Bresnick ( 88 )). After 6 h, transfection media was replaced with 10% SCM for 48 h. FRAP experiments were performed on an inverted Leica SP8 confocal microscope.…”

Pancreatic Ductal Adenocarcinoma Cortical Mechanics and Clinical Implications

“…Additionally, Ser-1943 phosphorylation is required for in vitro matrix degradation and increased invadopodia function, as well as increased in vivo metastasis. Therefore, NMIIA function regulates breast cancer cell invasion and metastasis ( 79 ). NMIIA-mediated cortical mechanics has also been implicated in colorectal cancer.…”