CHRONIC ALCOHOL EXPOSURE INCREASES GLYCOLYSIS AND CANCER STEMNESS OF OSCC THROUGH NFAT ACTIVATION
Chronic alcohol consumption is associated with cancer development and progression. Previous reports have demonstrated that cancer cell metabolism is heavily involved in the development of cancer, including a side population know as cancer stem cells (CSCs). Therefore, it is generally accepted targeting cancer cell metabolism may provide a new and effective method for the treatment of tumors. There are emerging reports of the effects of alcohol on glucose metabolism, however the effects of alcohol and cancer metabolism and its underlying mechanisms are not fully understood in cancers including OSCC. In this study, we investigated the local effect of alcohol on cancer cell metabolism and its underlying mechanism by which alcohol promotes oral cancer progression. We report chronic alcohol promotes malignant growth of OSCC. In addition, chronic alcohol treatment increased the rate of aerobic glycolysis. Increased aerobic glycolysis was required for the maintenance of CSC population as glycolysis inhibition suppressed CSC properties. In order to explore the molecular mechanism by which chronic alcohol induces glycolysis and stemness, we investigate the role of NFAT signaling as NFAT is known to be involved in glycolysis and malignant cancer properties. NFATc2 is upregulated in chronic EtOH treatment OSCC and is required for for EtOH mediated glycolysis and maintenance of CSC population. Our study suggests that NFATc2 may be a potential therapeutic target for eradicating CSCs in OSCC by suppressing glycolysis in alcohol related cancer patients.