title: Elucidation of how cancer cells avoid acidosis through comparative transcriptomic data analysis.
abstract: The rapid growth of cancer cells fueled by glycolysis produces large amounts of protons in cancer cells, which tri mechanisms to transport them out, hence leading to increased acidity in their extracellular environments. It has been well established that the increased acidity will induce cell death of normal cells but not cancer cells. The main question we address here is: how cancer cells deal with the increased acidity to avoid the activation of apoptosis. We have carried out a comparative analysis of transcriptomic data of six solid cancer types, breast, colon, liver, two lung (adenocarcinoma, squamous cell carcinoma) and prostate cancers, and proposed a model of how cancer cells utilize a few mechanisms to keep the protons outside of the cells. The model consists of a number of previously, well or partially, studied mechanisms for transporting out the excess protons, such as through the monocarboxylate transporters, V-ATPases, NHEs and the one facilitated by carbonic anhydrases. In addition we propose a new mechanism that neutralizes protons through the conversion of glutamate to γ-aminobutyrate, which consumes one proton per reaction. We hypothesize that these processes are regulated by cancer related conditions such as hypoxia and growth factors and by the pH levels, making these encoded processes not available to normal cells under acidic conditions.
authors: Computational Systems Biology Lab, University of Georgia, Athens, Georgia, United States of America.
authors: Kun
authors: K
authors: Xu
authors: Xizeng
authors: X
authors: Mao
authors: Minesh
authors: M
authors: Mehta
authors: Juan
authors: J
authors: Cui
authors: Chi
authors: C
authors: Zhang
authors: Fenglou
authors: F
authors: Mao
authors: Ying
authors: Y
authors: Xu
mesh_terms: D002256:Carbonic Anhydrases / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011522:Protons; D012964:Sodium / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D011522:Protons; D012964:Sodium; D025262:Vacuolar Proton-Translocating ATPases; D002256:Carbonic Anhydrases
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