Collectively, these findings indicate that URGCP plays an important role in promoting NSCLC cell invasion and metastasis by enhancing NF-κB-activated MMP-9 expression and may serve as a potential therapeutic target and prognostic marker.
We have recently shown that Semaphorin 4B (SEMA4B) inhibits the invasion of non-small cell lung cancer (NSCLC) through PI3K-dependent suppression of MMP9 activation.
Knockdown of GOLPH3 significantly suppressed the migratory and invasive ability of NSCLC cell lines and downregulated the enzyme activity and protein levels of MMP-2 and MMP-9.
To define the signal transduction cascades downstream of SEMA4b for regulation of MMP9 expression, we inhibited PI3K, ERK/MAPK, or JNK signaling pathway in SEMA4b knockout NSCLC and found that only inhibition of PI3K signaling pathway significantly decreased MMP9 activation.
The protein expression of LOX was measured by immunohistochemistry (IHC) in 110 paraffin-embedded tissues with NSCLC and the protein expression of MMP2/MMP9 was measured by in 30 NSCLC patients.
BTG1 expression decreased in NSCLC and correlated significantly with lymph node metastasis; clinical stage; histological grade; poor overall survival; cell proliferation; cell cycles; cell apoptosis; and migration and invasion in NSCLC cell by regulating CyclinD1, Bcl-2, and MMP-9 protein expression, suggesting that BTG1 may play important roles as a negative regulator to NSCLC cell.
Taken together, these findings suggest that EGF/EGFR signaling activates downstream PI3K/Akt to induce FoxO1 nuclear exclusion, which activates MMP9 to promote NSCLC invasiveness.
In addition, pretreatment of MG132 combined with IR significantly suppressed cell migration and invasion abilities in NSCLC cell lines, which was accompanied by decreased expression of matrix metalloproteinase (MMP)-2 and MMP-9 in NSCLC cell lines.
These findings support the hypothesis that the MMP9-1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length of survival in NSCLC patients.
Significantly, we show for the first time that CypA increased NSCLC cell invasion by regulating the activity of secreted matrix metallopeptidase 9 (MMP9).
Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression.
Prechemotherapy MMP-9 (ng/ml) levels were significantly higher in patients with advanced stage non-small cell lung cancer than in controls (7.2 ± 2.8 vs 4.5 ± 2.1, P <0.001).
In contrast, MMP-9 expression was higher in stage III-IV NSCLC cases compared to stage I-II tumors (p<0.05) and higher in NSCLC cases with metastasis than those without metastasis (p<0.05).
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).
In this study, we performed multivariate analysis of the mRNA levels of 10 selected genes [VEGF-A, VEGF121, VEGF165, VEGF189, S100A4, E-cadherin, Thrombospondin (TSP)-1, TSP-2, matrix metalloproteinase (MMP)-2, and MMP-9] in 130 NSCLC specimens using the real-time quantitative reverse transcription-polymerase chain reaction.
The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively).