Myosin light-chain kinase contributes to the proliferation and migration of breast cancer cells through cross-talk with activated ERK1/2.
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.
Zhou
Xiaolei
X
Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Liu
Yi
Y
You
Jiacong
J
Zhang
Hang
H
Zhang
Xiaodong
X
Ye
Lihong
L
D001381:Azepines / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D013997:Time Factors; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism
D001381:Azepines; C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; D056741:Cyclin D; D016213:Cyclins; D005419:Flavonoids; D051034:Inhibitor of Apoptosis Proteins; C489427:MYC protein, human; D008869:Microtubule-Associated Proteins; D018994:Myosin Light Chains; D009281:Naphthalenes; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D000077022:Survivin; D051176:beta Catenin; C070571:ML 7; D009219:Myosin-Light-Chain Kinase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one