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

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 ( 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.

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

“…Furthermore, HIF1A displayed promoter hypomethylation as well as increased expression in ATC compared with normal thyroid tissue. HIF1A is one of the main players in enabling cells to adapt to hypoxic conditions and has previously been reported to be highly expressed at the protein level in ATC [30,31]. Conversely, MAGI1 displayed promoter methylation as well as decreased expression in ATC compared with normal thyroid tissue (Table S1).…”

Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1

“…Reaching this "sweet spot" of optimal utilization of glucose that maximizes cell growth requires a well-coordinated rearrangement of cell metabolism. Although HIF-1α has long been recognized as a key player in response to hypoxia, hypoxia-independent mechanisms for HIF-1α signaling have also been recently reported when oxygen is available to the cell ("pseudohypoxic" conditions) [60].…”

Overexpression of HIF-1α and high density of tumor associated macrophages predict tumor aggression, invasion and unfavorable prognosis of Kazakh esophageal squamous cell carcinomas

“…Hypoxia is one of the most common stresses in the tumor microenvironment 4 , and hypoxia-inducible factor-1 (HIF-1) plays a crucial role in response to hypoxic stress 5 . The HIF-1 transcription factor complex consists of two subunits; an oxygensensitive HIF-1α subunit and a constitutively active HIF-1β subunit 6 .…”