Acid–base Homeostasis and Implications to the Phenotypic Behaviors of Cancer  

作　　者：Yi Zhou Wennan Chang Xiaoyu Lu Jin Wang Chi Zhang Ying Xu 

机构地区：[1]Cancer Systems Biology Center,China–Japan Union Hospital,Jilin University,Changchun 130033,China [2]Department of Biochemistry and Molecular Biology and Institute of Bioinformatics,University of Georgia,Athens,GA 30602,USA [3]Department of Medical and Molecular Genetics,Indiana University School of Medicine,Indianapolis,IN 46202,USA [4]Department of Electrical and Computer Engineering,Purdue University,West Lafayette,IN 47907,USA [5]Department of Biohealth Informatics,Indiana University–Purdue University Indianapolis,Indianapolis,IN 46202,USA [6]Departments of Chemistry and of Physics and Astronomy,Stony Brook University,Stony Brook,NY 11794,USA

出　　处：《Genomics, Proteomics & Bioinformatics》2023年第6期1133-1148,共16页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Science Foundation of USA(Grant No.2047631)and partially by Georgia Research Alliance,USA。

摘　　要：Acid–base homeostasis is a fundamental property of living cells,and its persistent disruption in human cells can lead to a wide range of diseases.In this study,we conducted a computational modeling analysis of transcriptomic data of 4750 human tissue samples of 9 cancer types in The Cancer Genome Atlas(TCGA)database.Built on our previous study,we quantitatively estimated the average production rate of OHby cytosolic Fenton reactions,which continuously disrupt the intracellular pH(pHi)homeostasis.Our predictions indicate that all or at least a subset of 43 reprogrammed metabolisms(RMs)are induced to produce net protons(H+)at comparable rates of Fenton reactions to keep the pHi stable.We then discovered that a number of wellknown phenotypes of cancers,including increased growth rate,metastasis rate,and local immune cell composition,can be naturally explained in terms of the Fenton reaction level and the induced RMs.This study strongly suggests the possibility to have a unified framework for studies of cancerinducing stressors,adaptive metabolic reprogramming,and cancerous behaviors.In addition,strong evidence is provided to demonstrate that a popular view that Na+/H+exchangers along with lactic acid exporters and carbonic anhydrases are responsible for the intracellular alkalization and extracellular acidification in cancer may not be justified.

关 键 词：Acid-basehomeostasis Cancer microenvironment Metabolic reprogramming Fenton reaction Ironmetabolism 

分 类 号：R730.2[医药卫生—肿瘤]