Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1α in cancer

Yoshihiro Hayashi, Asumi Yokota, Hironori Harada, Gang Huang

Research output: Contribution to journalReview articlepeer-review

112 Scopus citations

Abstract

Since the first identification of hypoxic cells in sections of carcinomas in the 1950s, hypoxia has been known as a central hallmark of cancer cells and their microenvironment. Indeed, hypoxia benefits cancer cells in their growth, survival, and metastasis. The historical discovery of hypoxia-inducible factor-1α (HIF1A) in the early 1990s had a great influence on the field as many phenomena in hypoxia could be explained by HIF1A. However, not all regions or types of tumors are necessarily hypoxic. Thus, it is difficult to explain whole cancer pathobiology by hypoxia, especially in the early stage of cancer. Upregulation of glucose metabolism in cancer cells has been well known. Oxygen-independent glycolysis is activated in cancer cells even in the normoxia condition, which is known as the Warburg effect. Accumulating evidence and recent advances in cancer metabolism research suggest that hypoxia-independent mechanisms for HIF signaling activation is a hallmark for cancer. There are various mechanisms that generate pseudohypoxic conditions, even in normoxia. Given the importance of HIF1A for cancer pathobiology, the pseudohypoxia concept could shed light on the longstanding mystery of the Warburg effect and accelerate better understanding of the diverse phenomena seen in a variety of cancers.

Original languageEnglish (US)
Pages (from-to)1510-1517
Number of pages8
JournalCancer Science
Volume110
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

Keywords

  • HIF1A
  • Warburg effect
  • hypoxia
  • oncometabolite
  • pseudohypoxia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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