High-mobility group box 1-mediated matrix metalloproteinase-9 expression in non-small cell lung cancer contributes to tumor cell invasiveness
Journal
American Journal of Respiratory Cell and Molecular Biology
Journal Volume
43
Journal Issue
5
Pages
530-538
Date Issued
2010
Author(s)
Liu P.-L.
Tsai J.-R.
Hwang J.-J.
Chou S.-H.
Cheng Y.-J.
Lin F.-Y.
Hung C.-Y.
Chen W.-C.
Chen Y.-H.
Chong I.-W.
Abstract
High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions. It is involved in invasion and metastasis in various human malignancies. However, the role of HMGB1 in non-small cell lung cancer (NSCLC) is unclear. We hypothesized that HMGB1 expression is a determinant of cellular invasiveness and metastasis in lung cancer. We examined HMGB1 expression in 48 NSCLC specimens by quantitative real-time PCR. High HMGB1 expression was significantly associated with clinically advanced stages (stage III-IV) (P < 0.05) and was correlated to expression of matrix metalloproteinase-9 (MMP-9) (P < 0.05). Patients with high levels of HMGB1 expression had poorer clinical prognosis. The expression level of MMP-9 and metastatic ability in vitro were significantly higher in an HMGB1-overexpressing human NSCLC cell lines (A549 and H23). The treatment with HMGB1 small interfering RNA reduced MMP-9 expression and the cellular metastatic ability in NSCLC cells. We also demonstrated that phosphoinositide 3-kinase/Akt and NF-κB-related pathways contributed to the HMGB1-induced MMP-9 expression and cellular metastatic ability.
SDGs
Other Subjects
gelatinase A; gelatinase B; high mobility group B1 protein; immunoglobulin enhancer binding protein; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; phosphatidylinositol 3 kinase; protein kinase B; small interfering RNA; stress activated protein kinase 1; gelatinase A; gelatinase B; high mobility group B1 protein; immunoglobulin enhancer binding protein; messenger RNA; mitogen activated protein kinase; MMP2 protein, human; phosphatidylinositol 3 kinase; protein kinase B; adult; advanced cancer; aged; article; cancer survival; cell invasion; cell migration; clinical article; controlled study; enzyme activity; female; gene expression; gene silencing; human; human cell; human tissue; lung non small cell cancer; male; metastasis; metastasis potential; prognosis; protein expression; cancer invasion; cell motion; enzyme activation; enzymology; gene expression regulation; genetics; lung tumor; metabolism; middle aged; pathology; tumor cell line; 1-Phosphatidylinositol 3-Kinase; Adult; Aged; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; HMGB1 Protein; Humans; Lung Neoplasms; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Mitogen-Activated Protein Kinases; Neoplasm Invasiveness; NF-kappa B; Proto-Oncogene Proteins c-akt; RNA, Messenger
Type
journal article