Progressive inactivation of GSK3β may promote enhanced EMT and oral cancer. GSK3β regulates several molecules that participate in epithelial-mesenchymal transformation, invasion and metastasis in cancer. Normal epithelial cells are connected to each other by E-cadherin, which binds to α- and β-catenin, which in turn connect E-cadherin to the actin cytoskeleton. Levels of E-cadherin are decreased in EMT. E-cadherin expression is suppressed by Snail. MMPs degrade the BM and facilitate the migration of cancer cells. Several MMPs upregulated and activated in OSCC are controlled by TFs such as Snail, AP-1, and NFκB. All of these events are directly or indirectly linked to the inactivation status of GSK3β.
Mishra Molecular Cancer 2010 9:144 doi:10.1186/1476-4598-9-144