Open AccessHypoxia/pseudohypoxia‐mediated activation of hypoxia‐inducible factor‐1α in cancer
Author(s) -
Hayashi Yoshihiro,
Yokota Asumi,
Harada Hironori,
Huang Gang
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13990
Subject(s) - hypoxia (environmental) , warburg effect , cancer cell , cancer , metastasis , tumor microenvironment , glycolysis , cancer research , biology , hypoxia inducible factors , downregulation and upregulation , hif1a , tumor hypoxia , microbiology and biotechnology , medicine , metabolism , angiogenesis , chemistry , endocrinology , biochemistry , oxygen , tumor cells , genetics , gene , radiation therapy , organic chemistry
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 ( HIF 1A) in the early 1990s had a great influence on the field as many phenomena in hypoxia could be explained by HIF 1A. 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 HIF 1A 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.