TY - JOUR
T1 - Hypoxia and oxygen-sensing signaling in gene regulation and cancer progression
AU - Yang, Guang
AU - Shi, Rachel
AU - Zhang, Qing
N1 - Funding Information:
Authors would like to thank the supports from the following funding resources (to Q.Z): Department of Defense Kidney Cancer Research Program Idea Development Award (W81XWH1910813), Kidney Cancer Research Alliance (KCCure), Cancer Prevention and Research Institute of Texas (CPRIT, RR190058), the National Cancer Institute (R01CA211732), American Cancer Society (RSG-18-059-01-TBE). Q.Z also is supported by a Kidney Cancer SPORE Developmental Research Award from UT Southwestern (P50 CA196516). Q.Z is an American Cancer Society Research Scholar, V Scholar, Kimmel Scholar, Susan G. Komen Career Catalyst awardee and Mary Kay Foundation awardee.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression. The key molecules of the hypoxia/oxygen-sensing signaling include the transcriptional regulator hypoxia-inducible factor (HIF) which widely controls oxygen responsive genes, the central members of the 2-oxoglutarate (2-OG)-dependent dioxygenases, such as prolyl hydroxylase (PHD or EglN), and an E3 ubiquitin ligase component for HIF degeneration called von Hippel–Lindau (encoding protein pVHL). In this review, we summarize the current knowledge about the canonical hypoxia signaling, HIF transcription factors, and pVHL. In addition, the role of 2-OG-dependent enzymes, such as DNA/RNA-modifying enzymes, JmjC domain-containing enzymes, and prolyl hydroxylases, in gene regulation of cancer progression, is specifically reviewed. We also discuss the therapeutic advancement of targeting hypoxia and oxygen sensing pathways in cancer.
AB - Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression. The key molecules of the hypoxia/oxygen-sensing signaling include the transcriptional regulator hypoxia-inducible factor (HIF) which widely controls oxygen responsive genes, the central members of the 2-oxoglutarate (2-OG)-dependent dioxygenases, such as prolyl hydroxylase (PHD or EglN), and an E3 ubiquitin ligase component for HIF degeneration called von Hippel–Lindau (encoding protein pVHL). In this review, we summarize the current knowledge about the canonical hypoxia signaling, HIF transcription factors, and pVHL. In addition, the role of 2-OG-dependent enzymes, such as DNA/RNA-modifying enzymes, JmjC domain-containing enzymes, and prolyl hydroxylases, in gene regulation of cancer progression, is specifically reviewed. We also discuss the therapeutic advancement of targeting hypoxia and oxygen sensing pathways in cancer.
KW - HIFs
KW - Hypoxia
KW - JmjCs
KW - PHDs
KW - TETs
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U2 - 10.3390/ijms21218162
DO - 10.3390/ijms21218162
M3 - Review article
C2 - 33142830
AN - SCOPUS:85094807680
SN - 1661-6596
VL - 21
SP - 1
EP - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 21
M1 - 8162
ER -