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Cancers 2013, 5(1), 15-26; doi:10.3390/cancers5010015

The Critical Impact of HIF-1a on Gastric Cancer Biology

1,2,*  and 3
1 Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan 2 Department of Surgery, NHO Higashisaga Hospital, Saga 849-0101, Japan 3 Saga University Faculty of Medicine, Saga 849-8501, Japan
* Author to whom correspondence should be addressed.
Received: 26 November 2012 / Revised: 21 December 2012 / Accepted: 5 January 2013 / Published: 10 January 2013
(This article belongs to the Special Issue Gastric Cancer)
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Hypoxia inducible factor-1 (HIF-1) monitors the cellular response to the oxygen levels in solid tumors. Under hypoxia conditions, HIF-1a protein is stabilized and forms a heterodimer with the HIF-1β subunit. The HIF-1 complex activates the transcription of numerous target genes in order to adapt the hypoxic environment in human cancer cells. In gastric cancer patients, HIF-1a activation following extended hypoxia strongly correlates with an aggressive tumor phenotype and a poor prognosis. HIF-1a activation has been also reported to occur via hypoxia-independent mechanisms such as PI3K/AKT/mTOR signaling and ROS production. This article argues for the critical roles of HIF-1a in glucose metabolism, carcinogenesis, angiogenesis, invasion, metastasis, cell survival and chemoresistance, focusing on gastric cancer.
Keywords: HIF-1a; hypoxia; gastric cancer HIF-1a; hypoxia; gastric cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kitajima, Y.; Miyazaki, K. The Critical Impact of HIF-1a on Gastric Cancer Biology. Cancers 2013, 5, 15-26.

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