P5-07-03: Modulation of Autophagic Activity by Extracellular pH.

Reprogramming energy metabolism from oxidative phosphorylation to aerobic glycolysis, a common feature of human cancer, results in a relative acidic tumor microenvironment which is further accentuated by hypoxia operating within most tumors. We report that alteration of extracellular pH induces marked and rapid changes of autophagic activity in a variety of cell lines including mammary non-transformed cells and breast cancer cells. Interestingly, acidic and basic conditions induce completely opposite effect on autophagy, with its activity suppressed at lower pH whereas stimulated at higher pH. Gene knockdown experiments indicate that pH induced-autophagy requires Beclin 1, Vps34 and ATG5, key components of the autophagy pathway. Of note, acidic condition not only inhibits the basal but also blocks starvation-induced autophagy activity. Significantly, examination of different areas of tumor mass reveals a lower autophagic activity within the inner region than the outer region. These findings have important implications on the connections between autophagy and cancer as well as a wide range of other physiological and pathological processes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-03.