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The Critical Impact of HIF-1a on Gastric Cancer Biology
Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
Department of Surgery, NHO Higashisaga Hospital, Saga 849-0101, Japan
Saga University Faculty of Medicine, Saga 849-8501, Japan
* Author to whom correspondence should be addressed.
Received: 26 November 2012; in revised form: 21 December 2012 / Accepted: 5 January 2013 / Published: 10 January 2013
Abstract: 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
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MDPI and ACS Style
Kitajima, Y.; Miyazaki, K. The Critical Impact of HIF-1a on Gastric Cancer Biology. Cancers 2013, 5, 15-26.
Kitajima Y, Miyazaki K. The Critical Impact of HIF-1a on Gastric Cancer Biology. Cancers. 2013; 5(1):15-26.
Kitajima, Yoshihiko; Miyazaki, Kohji. 2013. "The Critical Impact of HIF-1a on Gastric Cancer Biology." Cancers 5, no. 1: 15-26.