Figure 3.

Progressive inactivation of GSK3β may promote increased anti-apoptosis and oral cancer. GSK3β-mediated signaling controls apoptosis in OSCC. In the intrinsic apoptotic pathway, inactive GSK3β fails to promote apoptosis by the disruption of mitochondrial membrane potential resulting from disruption of the Bcl-2/Bax ratio. Overexpression of Bcl-2 and suppression of Bax occur frequently in OSCC. This may be due to either inactive p53 (in the subgroup of cases in which p53 is not mutated or silenced) or active CREB; both are controlled by GSK3β. In the extrinsic pathway, active GSK3β promotes apoptosis by inducing procaspase-8 activation. Moreover, the inactivated GSK3β might send survival signals via the extrinsic pathway by blocking procaspase-8 activation in OSCC. By doing this, GSK3β might maintain the balance between proliferation and death and contribute to tissue homeostasis in normal oral epithelium; these might be perturbed in OSCC.