Myosin Light-Chain Kinase Contributes to the Proliferation and Migration of Breast Cancer Cells Through Cross-Talk With Activated ERK1/2

Cancer Lett. 2008 Nov 8;270(2):312-27. doi: 10.1016/j.canlet.2008.05.028. Epub 2008 Aug 16.

Abstract

Myosin light-chain kinase (MLCK) plays a crucial role in the cell migration and tumor metastasis. Herein, we investigated the signaling pathways involved in MLCK using ML-7, a specific inhibitor of MLCK, in breast cancer cell proliferation and migration. Our data showed that reduction of MLCK in breast cancer cells mediated by 20 microM ML-7 was able to depress the cell proliferation and migration using two parallel cell lines (MCF-7 and LM-MCF/MDA-MB-231) with different metastatic abilities through reciprocal cross-talk with activated ERK1/2, in which both phosphorylated myosin light chain (p-MLC) and cascades of beta-catenin, cyclin D1, survivin, and c-Myc serve as essential downstream effectors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / pharmacology
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Cyclin D
  • Cyclins / metabolism
  • Female
  • Flavonoids / pharmacology
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Myosin Light Chains / metabolism
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Myosin-Light-Chain Kinase / metabolism*
  • Naphthalenes / pharmacology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction* / drug effects
  • Survivin
  • Time Factors
  • Transfection
  • beta Catenin / metabolism

Substances

  • Azepines
  • BIRC5 protein, human
  • CTNNB1 protein, human
  • Cyclin D
  • Cyclins
  • Flavonoids
  • Inhibitor of Apoptosis Proteins
  • MYC protein, human
  • Microtubule-Associated Proteins
  • Myosin Light Chains
  • Naphthalenes
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-myc
  • Survivin
  • beta Catenin
  • ML 7
  • Myosin-Light-Chain Kinase
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one