ArticleCell systems2022
Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells.
Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- PHGDH loss promotes hypoxia tolerance through glycolytic reprogramming and enhanced HIF-1 activity.Cell death discovery · 2026Article
- HIF-1α Signaling in Uterine Fibroids: A Central Integrator of Hypoxic, Hormonal, and Fibrotic Pathways.Oxygen (Basel, Switzerland) · 2026Article
- Stress-responsive membrane proteins as execution nodes of tumor cell adaptation to microenvironmental stress.Oncogene · 2026Review
- Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Hif-1 responsive IFFLs to explain specific transcriptional responses to cycling hypoxia in cancers.NPJ systems biology and applications · 2025Article
- Lactate and gastric cancer immunotherapy from regulatory mechanisms to therapeutic strategies: a critical review.European journal of medical research · 2025Review
- Life in the fast lane: Functional consequences of male-female dynamic differences in the renal auto-regulation of flow.bioRxiv : the preprint server for biology · 2025Article
- Inherent single-cell heterogeneity of the transcriptional response to hypoxia in cancer cells.NAR cancer · 2025Article
- Development and experimental verification of a prognosis model for hypoxia- and lactate metabolism-associated genes in HNSCC.Medicine · 2025Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Oscillatory hypoxia induced gene expression predicts low survival in human breast cancer patients.Molecular carcinogenesis · 2024Article
- Elucidating the spatiotemporal dynamics of glucose metabolism with genetically encoded fluorescent biosensors.Cell reports methods · 2024Review
- Stable and oscillatory hypoxia differentially regulate invasibility of breast cancer associated fibroblasts.Mechanobiology in medicine · 2024Article
- The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia.Nature cancer · 2024Article
- Lactate in breast cancer cells is associated with evasion of hypoxia-induced cell cycle arrest and adverse patient outcome.Human cell · 2024Article
- Tissue-of-origin for cancers determines HIF-1 activation induced phenotypic heterogeneity.Molecular carcinogenesis · 2024Article
- Article
- Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors.Cancers · 2023Article
- Molecular Mechanisms of Western Diet-Induced Obesity and Obesity-Related Carcinogenesis-A Narrative Review.Metabolites · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Response to hypoxia is a highly regulated process, but little is known about single-cell responses to hypoxic conditions. Using fluorescent reporters of hypoxia response factor-1α (HIF-1α) activity in various cancer cell lines and patient-derived cancer cells, we show that hypoxic responses in individual cancer cells can be highly dynamic and variable. These responses fall into three classes, including oscillatory activity. We identify a molecular mechanism that can account for all three response classes, implicating reactive-oxygen-species-dependent chaperone-mediated autophagy of HIF-1α in a subset of cells. Furthermore, we show that oscillatory response is modulated by the abundance of extracellular lactate in a quorum-sensing-like mechanism. We show that oscillatory HIF-1α activity rescues hypoxia-mediated inhibition of cell division and causes broad suppression of genes downregulated in cancers and activation of genes upregulated in many cancers, suggesting a mechanism for aggressive growth in a subset of hypoxic tumor cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.