HIF-1α-mediated metabolic reprogramming in hypoxia-driven tumor metastasis
5 affiliations
- 1School of Basic Medicine/Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Gannan Medical University, Ganzhou, Jiangxi, China
- 2School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, China
- 3School of Medical Information Engineering/Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province, Gannan Medical University, Ganzhou, Jiangxi, China
- 4Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education/School of Pharmacy, Gannan Medical University, Ganzhou, China
- 5Scientific Research Center, Gannan Medical University, Ganzhou, Jiangxi, China
Abstract
Tumor metastasis is a multistep process that requires profound metabolic plasticity to support cancer cell invasion, survival in circulation, colonization of distant organs, and metastatic outgrowth. Hypoxia is a hallmark of solid tumors and a major driver of metastatic progression. As a central transcriptional regulator of the hypoxic response, hypoxia-inducible factor-1α is stabilized under oxygen deprivation and orchestrates broad metabolic reprogramming by regulating glycolysis, lactate production and export, mitochondrial respiration, lipid metabolism, amino acid utilization, redox homeostasis, and interactions with the tumor microenvironment. These metabolic adaptations not only provide bioenergetic and biosynthetic support for disseminating cancer cells but also promote epithelial-mesenchymal transition, extracellular matrix remodeling, angiogenesis, immune evasion, and premetastatic niche formation. In this review, we summarize current knowledge regarding the mechanisms by which hypoxia-inducible factor-1α-mediated metabolic reprogramming contributes to different stages of the metastatic cascade. We also discuss the therapeutic potential and limitations of targeting hypoxia-inducible factor-1α-associated metabolic vulnerabilities in metastatic cancer. A better understanding of the context-dependent functions of hypoxia-inducible factor-1α may facilitate the development of more effective anti-metastatic strategies.
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BibTeX
@article{shao2026hif1αmediated,
title = {{HIF-1α-mediated metabolic reprogramming in hypoxia-driven tumor metastasis}},
author = {Shulun Shao and Mengxin Wang and Renjian Xie and Shenglan Liu and Wei Dai and Tai Zeng and Lei Lai and Kunpeng Zhang and Yumei Li},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1997123},
url = {https://doi.org/10.3389/fcell.2026.1997123},
note = {CC BY},
}
RIS
TY - JOUR
TI - HIF-1α-mediated metabolic reprogramming in hypoxia-driven tumor metastasis
AU - Shulun Shao
AU - Mengxin Wang
AU - Renjian Xie
AU - Shenglan Liu
AU - Wei Dai
AU - Tai Zeng
AU - Lei Lai
AU - Kunpeng Zhang
AU - Yumei Li
PY - 2026
DA - 2026/10/28
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1997123
UR - https://doi.org/10.3389/fcell.2026.1997123
AB - Tumor metastasis is a multistep process that requires profound metabolic plasticity to support cancer cell invasion, survival in circulation, colonization of distant organs, and metastatic outgrowth. Hypoxia is a hallmark of solid tumors and a major driver of metastatic progression. As a central transcriptional regulator of the hypoxic response, hypoxia-inducible factor-1α is stabilized under oxygen deprivation and orchestrates broad metabolic reprogramming by regulating glycolysis, lactate production and export, mitochondrial respiration, lipid metabolism, amino acid utilization, redox homeostasis, and interactions with the tumor microenvironment. These metabolic adaptations not only provide bioenergetic and biosynthetic support for disseminating cancer cells but also promote epithelial-mesenchymal transition, extracellular matrix remodeling, angiogenesis, immune evasion, and premetastatic niche formation. In this review, we summarize current knowledge regarding the mechanisms by which hypoxia-inducible factor-1α-mediated metabolic reprogramming contributes to different stages of the metastatic cascade. We also discuss the therapeutic potential and limitations of targeting hypoxia-inducible factor-1α-associated metabolic vulnerabilities in metastatic cancer. A better understanding of the context-dependent functions of hypoxia-inducible factor-1α may facilitate the development of more effective anti-metastatic strategies.
SN - 2296-634X
ER -