A role for focal adhesion kinase in hyluronan-dependent MMP-2 secretion in a human small-cell lung carcinoma cell line, QG90.
Hyluronan (HA), a nonsulfated high-molecular mass glycoaminoglycan, has been assigned as a clinical marker for the progression of various tumors. We found that HA stimulation of QG90, a cell line derived from human small-cell lung carcinoma, activates the secretion of matrix metalloproteinase-2 (MMP-2) in a focal adhesion kinase (FAK)-dependent manner. HA stimulation of QG90 cells activated MMP-2 secretion in a time-dependent manner. Larger sizes of HA seemed to have higher activities than smaller size one in MMP-2 secretion. Under HA stimulation, tyrosine phosphorylation of cellular proteins including FAK was activated. By use of antisense oligonucleotide to FAK, we found that FAK signaling was required for the activation of MMP-2 secretion and for the sustained activation of MAP kinase by HA treatment. These results strongly suggest that FAK-MAPK signaling is involved, at least in part, in HA-dependent activation of MMP-2 secretion in QG90 cells.
Zhang
Yanying
Y
Laboratory of Molecular Pathogenesis, Nagoya University School of Medicine, Showaku, Nagoya, 466-8550, Japan.
Thant
Aye Aye
AA
Hiraiwa
Yukiko
Y
Naito
Yuko
Y
Sein
Thet Thet
TT
Sohara
Yasuyoshi
Y
Matsuda
Satoru
S
Hamaguchi
Michinari
M
D018288:Carcinoma, Small Cell / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D006820:Hyaluronic Acid; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2