Moreover, cyclin-D1, Bcl-2, and matrix metalloproteinase-9 (MMP-9) were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration.
Our data showed that curcumin treatment not only decreased the expression of MMP-2 and MMP-9 to inhibit invasiveness in oral cancer but also modulated the expression of EMT markers, such as Snail, Twist, and E-cadherin, and induced p53 expression that is crucial to EMT repression.
The observation that T allele carriers have an increased risk for developing oral cancer only in initial stages, but not in advanced ones, may be due to the role of MMP-9 in the inhibition of angiogenesis by generating angiostatin from plasminogen.
Finally, we searched our salivary proteomic database for increases in MMP-9 and discovered it was the third most significant protein in salivas of oral cavity cancer patients over normal controls.
Thus, our aim was to determine whether a functional MMP-9 polymorphism might also influence the risk or affect the progression of areca-associated oral cancers.