The role of HIF-1α in chemo-/radioresistant tumors

Abstract

Chemo-/radioresistance is a major obstacle in clinical oncology. The precise failure mechanisms of chemo-/radioresistance are multifactorial failures. It is now widely accepted that a tumor hypoxia microenvironment contributes significantly to chemo-/radioresistance. Hypoxia is the most common and obvious neoplastic microenvironment and is due to the rapid proliferation of tumor cells. HIF-1α is a principal molecular mediator of adaptability to hypoxia in tumor cells. HIF-1α activation leads to the transcription of a plethora of target genes that promote physiological changes associated with chemo-/radioresistance, including increasing the ability of DNA repair, the inhibition of apoptosis, and alterations of the cellular metabolism. Moreover, recent findings suggest that HIF-1α-activated autophagy is a crucial factor in the promotion of cell survival under the distressed microenvironment, thereby leading to the chemo-/radioresistance. This chapter presents an overview of the role of HIF-1α in chemo-/radioresistance of tumor cells.

The Roles of Hypoxia-Inducible Factors and Non-Coding RNAs in Gastrointestinal Cancer

“…It is well known that activating HIF signaling results in resistance to chemo-and radiotherapy in hypoxic cancer cells [75]. As mentioned previously, HIF-1α suppresses Bcl-2 expression in colon cancer cells by inducing miR-210 expression, resulting in autophagy activation and radioresistance [56].…”

Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish

“…Indeed, the activation of HIF1α is known to be associated with the resistance of various tumors to chemo and radio therapies by mechanisms that are extremely diverse and complex, e.g. [23]. Similarly, HIF1α was shown to provide the radioresistance in hypoxic mice mesenchymal stromal cells by upregulating DNA repair proteins [24].…”

Elevated HSP90 associates with expression of HIF‐1α and p‐AKT and is predictive of poor prognosis in nasopharyngeal carcinoma

“…Hypoxia inducible factor (HIF) is a crucial nuclear transcriptional complex that mediates cellular adaption to hypoxia stress. It is widely expressed in various mammalian tissues, and HIF‐1α is a member of the HIF complex as well as a biomarker of the hypoxia microenvironment . There are two types of pathways for the regulation of HIF‐1α expression: oxygen‐dependent and oxygen‐independent pathways.…”

“…It is widely expressed in various mammalian tissues, and HIF-1a is a member of the HIF complex as well as a biomarker of the hypoxia microenvironment. 8 There are two types of pathways for the regulation of HIF-1a expression: oxygen-dependent and oxygen-independent pathways. HSP90 regulates HIF-1a expression in an oxygen-dependent manner, leading to angiogenesis, metastasis and cell survival.…”