Roles of p53, Myc and HIF-1 in Regulating Glycolysis — the Seventh Hallmark of Cancer

Review

DOI: 10.1007/s00018-008-8224-x

Cite this article as:
Yeung, S.J., Pan, J. & Lee, MH. Cell. Mol. Life Sci. (2008) 65: 3981. doi:10.1007/s00018-008-8224-x

Abstract.

Despite diversity in genetic events in oncogenesis, cancer cells exhibit a common set of functional characteristics. Otto Warburg discovered that cancer cells have consistently higher rates of glycolysis than normal cells. The underlying mechanisms leading to the Warburg phenomenon include mitochondrial changes, upregulation of rate-limiting enzymes/proteins in glycolysis and intracellular pH regulation, hypoxia-induced switch to anaerobic metabolism, and metabolic reprogramming after loss of p53 function. The regulation of energy metabolism can be traced to a “triad” of transcription factors: c-MYC, HIF-1 and p53. Oncogenetic changes involve a nonrandom set of gene deletions, amplifications and mutations, and many oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and interaction with diabetes mellitus. Many drugs targeting energy metabolism are in development. Future advances in technology may bring about transcriptome and metabolome-guided chemotherapy.

Keywords.

Oncogenes tumor suppressors signaling pathways mTOR MYC p53 HIF-1 glycolysis Warburg phenomenon 

Copyright information

© Birkhäuser Verlag, Basel 2008

Authors and Affiliations

  1. 1.Department of General Internal Medicine, Ambulatory Treatment and Emergency CareThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Endocrine Neoplasia and Hormonal DisordersThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Molecular and Cellular OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  4. 4.Department of PathophysiologySun Yat-Sen University Medical School, GuangzhouGuangzhouChina

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