HSP27 regulates cell adhesion and invasion via modulation of focal adhesion kinase and MMP-2 expression.
Heat-shock protein 27 (HSP27), a member of the small heat-shock protein family, is a molecule involved in cellular protection in response to a variety of stresses such as heat shock, toxicants, and oxidative stress. HSP27 is also known to modulate cell functions via interaction with the actin cytoskeleton. To elucidate the functions of HSP27 in adhesion and invasion in more detail, we examined NIH3T3 cells overexpressing HSP27. HSP27 overexpression affected FAK phosphorylation and focal adhesion formation, depending on integrin-mediated actin cytoskeleton polymerization. In addition, the HSP27-overexpressing cells showed a retarded cell migration and invasion in wound-healing assays. Such HSP27-mediated retarded wound healing was correlated with reduced matrix metalloproteinase-2 (MMP-2) expression. The transcription factor for MMP-2 expression, signal transducer and activator or transcription 3 (STAT3), was correspondingly less phosphorylated. When a phosphomimetic form of HSP27 was transiently transfected, migration and invasion were similarly decreased via the regulation of the FAK/STAT3/MMP-2 signaling pathway, whereas a non-phosphorylatable form of HSP27 blocked HSP27-mediated phenotypes probably due to a dominant-negative effect on phosphorylation of endogenous HSP27. Altogether, our results suggest that HSP27 can enhance cell adhesion and modulate cell migration and invasion via the coordination of FAK-dependent actin organization and STAT3-dependent MMP-2 expression, and that phosphorylation of HSP27 is indispensable to regulate this signal pathway.
Lee
Joong-Won
JW
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Kwak
Hee-Jin
HJ
Lee
Je-Jung
JJ
Kim
Yong-Nyun
YN
Lee
Jung Weon
JW
Park
Myung-Jin
MJ
Jung
Seung Eun
SE
Hong
Seok-Il
SI
Lee
Jeong-Hwa
JH
Lee
Jae-Seon
JS
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D015536:Down-Regulation; D005347:Fibroblasts / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014945:Wound Healing
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D016023:Integrins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse