Correlation between Loss of E-cadherin, Matrix-metalloproteinases and c-Jun expression in Oral Carcinogenesis

Abstract

Background: Earlier invitro studies have observed that loss of E-cadherin is responsible for progression and metastasis of cancer by upregulation of c-Jun protein. There being lack of simultaneous evaluation of matrix metalloproteinase (MMP) -2 and -9, E-cadherin and c-Jun mRNA and protein.Objective: This study aimed to correlate the above-mentioned parameters to evaluate the pathway of oral carcinogenesis. Methods:The study included 100 controls, 50 patients with oral precancerous conditions (OPC) and 100 oral cancer patients. MMPs were evaluated by gelatin zymography, ECAD and CJUN mRNA and protein expression by semi quantitative RT-PCR and western blot respectively. Results:The levels of active and total MMP-2 and MMP-9 were significantly higher in patients with OPC and oral cancer patients as compared to controls. A significant increase in truncated E-cadherin and c-Jun protein was observed in malignant tissues as compared to adjacent normal tissues while CJUN mRNA levels were comparable. Higher values of c-Jun protein and MMPs, and lower values of ECAD mRNA were associated with reduced overall survival. A positive correlation was observed between truncated E-cadherin, MMPs and c-Jun protein. Conclusions:MMPs modulate cell-cell adhesion by increasing truncation of E-cadherin resulting in loss of Ecadherin which is responsible for upregulation of c-Jun protein in oral cancer.