HIF-1-regulated glucose metabolism in the control of apoptosis signaling

Abstract

Resistance of human cancers to current treatment approaches remains a major concern in oncology. Therefore, much effort has been focused on identifying molecular pathways that are responsible for primary or acquired resistance of cancers in order to overcome resistance. Hypoxia is one of the hallmarks of solid tumors and usually correlates with poor prognosis. Under hypoxic conditions, cancer cells undergo a variety of adoptive changes, including the activation of signaling pathways, which promote cancer cell survival and block cell death. Hypoxia inducible factor (HIF)-1 is the key transcription factor that mediates adaptation of cancer cells to the hypoxic environment. There is increasing evidence that HIF-1 promotes tumor growth, at least in part, by upregulating genes that are involved in cellular energy metabolism. Thus, HIF-1 and hypoxia-inducible genes represent attractive targets for the design of molecular targeted therapies, which may offer new therapeutic options for a wide range of malignancies.

Keywords::

• apoptosis
• cancer
• HIF-1α
• hypoxia
• glucose metabolism

Financial & competing interests disclosure

Work in the author’s laboratory is supported by grants from the Deutsche Forschungsgemeinschaft, the Deutsche Krebshilfe, the Bundesministerium für Forschung und Technologie, DAAD, Else-Kröner-Fresenius Stiftung, Interuniversity Attraction Pole 6/18 and the European Community. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.