Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis

Laura E. Norwood Toro, Yarong Wang, John S. Condeelis, Joan G. Jones, Jonathan M. Backer, Anne R. Bresnick

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalExperimental Cell Research
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Nonmuscle Myosin Type IIA
Myosin Heavy Chains
Phosphorylation
Neoplasm Metastasis
Neoplasms
Breast Neoplasms
Myosin Type II
Epidermal Growth Factor
Extracellular Matrix

Keywords

  • Invadopodia
  • Invasion
  • Matrix degradation
  • Myosin-II
  • Phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

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title = "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.",
keywords = "Invadopodia, Invasion, Matrix degradation, Myosin-II, Phosphorylation",
author = "{Norwood Toro}, {Laura E.} and Yarong Wang and Condeelis, {John S.} and Jones, {Joan G.} and Backer, {Jonathan M.} and Bresnick, {Anne R.}",
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T1 - Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis

AU - Norwood Toro, Laura E.

AU - Wang, Yarong

AU - Condeelis, John S.

AU - Jones, Joan G.

AU - Backer, Jonathan M.

AU - Bresnick, Anne R.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Invadopodia

KW - Invasion

KW - Matrix degradation

KW - Myosin-II

KW - Phosphorylation

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