Overexpression of carbonic anhydrase IX induces cell motility by activating matrix metalloproteinase-9 in human oral squamous cell carcinoma cells

Abstract

Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells. In addition, CAIX overexpression increased the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9) and the phosphorylation of focal adhesion kinase (FAK), steroid receptor coactivator (Src), and extracellular signal-regulated kinase 1/2 signaling proteins. CAIX overexpression also increased the binding capacity of nuclear factor-κB (NF-κB), c-Jun, and c-Fos on the MMP-9 gene promoter. In addition, treatment with MMP-9 short hairpin RNA, an MMP inhibitor (GM6001), an FAK mutant, or an MEK inhibitor (U0126) inhibited CAIX-induced cell motility in SCC-9 cells. Moreover, data sets from The Cancer Genome Atlas demonstrated that CAIX expression was significantly associated with advanced progression and poor survival in oral cancer. In conclusion, it can be inferred that CAIX overexpression induces MMP-9 gene expression, which consequently induces the metastasis of oral cancer cells.

Geraniin inhibits oral cancer cell migration by suppressing matrix metalloproteinase‐2 activation through the FAK/Src and ERK pathways

“…The Src and MAPK pathways have been reported to be involved in the upstream signaling pathways of MMP‐2 expression and cancer metastasis . Therefore, the effects of geraniin on the expression of Src and MAPK pathways were investigated to elucidate their underlying mechanisms.…”

“…The Src and MAPK pathways have been reported to be involved in the upstream signaling pathways of MMP-2 expression and cancer metastasis. 16,32,33 Therefore, the effects of geraniin on the expression of Src and MAPK pathways were investigated to elucidate their underlying mechanisms. The results of the Western blot assay revealed that the phosphorylation of Src, focal adhesion kinase (FAK), and ERK1/2 decreased in SCC-9 cells but not the phosphorylation of the JNK1/2 and p38 pathways ( Figure 5).…”

Antimetastatic potentials of salvianolic acid A on oral squamous cell carcinoma by targeting MMP‐2 and the c‐Raf/MEK/ERK pathway

“…MMP‐2 is highly observed in metastatic cases of OSCC, and its expression and activity against ECM during metastasis have been linked to the promotion of cell metastasis . Earlier reports have indicated that the mitogen‐activated protein kinase kinase (MEK)/mitogen‐activated protein kinase (MAPK) family and the focal adhesion kinase (FAK)‐Src pathway are critical points in the regulation of cell migration, invasion, adhesion, proliferation, and MMP expression …”

Effects of dihydromyricetin on ARPE‐19 cell migration through regulating matrix metalloproteinase‐2 expression

“…MMPs regulate ECM to facilitate cell migration by removing barriers. Specifically, the expressions of MMP‐2 and MMP‐9 are associated with the invasive potential of cancer . Previous studies also reported that epigallocatechin gallate prevents transforming growth factor beta 1‐induced MMP‐2 in ARPE‐19 cells .…”

“…Specifically, the expressions of MMP-2 and MMP-9 are associated with the invasive potential of cancer. 9,11,12 Previous studies also reported that epigallocatechin gallate prevents transforming growth factor beta 1-induced MMP-2 in ARPE-19 cells. 13 Moreover, studies have reported that MMP-2 expression correlates significantly with the PVR grade.…”