'The metabolism of tumours': 70 years later

Gregg L. Semenza, Dmitri Artemov, Atul Bedi, Zaver Bhujwalla, Kelly Chiles, David Feldser, Erik Laughner, Rajani Ravi, Jonathan Simons, Panthea Taghavi, Hua Zhong

Research output: Contribution to journalArticle

Abstract

Otto Warburg's classic treatise on the reprogramming of tumour metabolism from oxidative to glycolytic metabolism was published in London in 1930. Although the Warburg effect is one of the most universal characteristics of solid tumours, the molecular basis for this phenomenon has only recently been elucidated by studies indicating that increased expression of genes encoding glucose transporters and glycolytic enzymes in tumour cells is mediated by the transcription factors c-MYC and HIF-1. Whereas c-myc is a direct target for oncogenic mutations, expression of hypoxia-inducible factor 1 (HIF-1) is indirectly up-regulated via gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes that result in increased HIF-1α protein expression and/or increased HIF-1 transcriptional activity in a cell-type-specific manner. As a result of genetic alterations and intratumoral hypoxia, HIF-1α is overexpressed in the majority of common human cancers relative to the surrounding normal tissue. In human breast cancer and brain tumours, HIF-1α overexpression is strongly correlated with tumour grade and vascularity.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalNovartis Foundation Symposium
Volume240
StatePublished - Dec 1 2001

ASJC Scopus subject areas

  • Medicine(all)

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    Semenza, G. L., Artemov, D., Bedi, A., Bhujwalla, Z., Chiles, K., Feldser, D., Laughner, E., Ravi, R., Simons, J., Taghavi, P., & Zhong, H. (2001). 'The metabolism of tumours': 70 years later. Novartis Foundation Symposium, 240, 251-260.