ArticleMolecular cancer research : MCR2019
HILPDA Regulates Lipid Metabolism, Lipid Droplet Abundance, and Response to Microenvironmental Stress in Solid Tumors.
Article in Molecular cancer research : MCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- HILPDA, Regulated by WTAP in an m6A-Dependent Manner, Enhances Osteosarcoma Development by Inhibiting Ferroptosis and Promoting Glycolysis.Biochemical genetics · 2026Article
- Lipidomic Remodeling by HILPDA in Granulosa Cells Impairs Ovarian Reserve Through Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Select intratumoral riboflavin-auxotrophicProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Fatty Acid Metabolism and Hypoxia in the Tumor Microenvironment: Metabolic Adaptation and Clinical Potential in Colorectal Cancer.Biomedicines · 2026Review
- Article
- Prognostic and Therapeutic Potential of Nicotinamide N-Methyltransferase and Hypoxia Inducible Lipid Droplet Associated in Clear Cell Renal Cell Carcinoma.Journal of Korean medical science · 2025Article
- Navigating lipid droplet proteins - part I: ER targeting routes of lipid droplet-destined membrane proteins.Biochemical Society transactions · 2025Review
- Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies.Medical oncology (Northwood, London, England) · 2025Review
- Kinsenoside Suppresses DGAT1-Mediated Lipid Droplet Formation to Trigger Ferroptosis in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- HIG-2 promotes glioma stemness and radioresistance mediated by IGFBP2-rich microparticles in hypoxia.Apoptosis : an international journal on programmed cell death · 2025Article
- Metabolic ripple effects - deciphering how lipid metabolism in cancer interfaces with the tumor microenvironment.Disease models & mechanisms · 2024Review
- CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α.Cell death & disease · 2024Article
- Prognostic Hypoxia-Angiogenesis-Related Gene Signature in Hepatocellular Carcinoma, in Which HILPDA Contributes to Tumor Progression.Journal of inflammation research · 2024Article
- Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- A novel ferroptosis-related microRNA signature with prognostic value in osteosarcoma.Acta biochimica et biophysica Sinica · 2023Article
- Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status.Bone research · 2023Article
- Applications of organoid technology to brain tumors.CNS neuroscience & therapeutics · 2023Review
- HILPDA-mediated lipidomic remodelling promotes radiotherapy resistance in nasopharyngeal carcinoma by accelerating mitophagy.Cellular and molecular life sciences : CMLS · 2023Article
- HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia.Journal of hepatology · 2023Article
- Genome-Wide Association Analysis of Muscle pH in Texel Sheep × Altay Sheep FAnimals : an open access journal from MDPI · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Accumulation of lipid droplets has been observed in an increasing range of tumors. However, the molecular determinants of this phenotype and the impact of the tumor microenvironment on lipid droplet dynamics are not well defined. The hypoxia-inducible and lipid droplet associated protein HILPDA is known to regulate lipid storage and physiologic responses to feeding conditions in mice, and was recently shown to promote hypoxic lipid droplet formation through inhibition of the rate-limiting lipase adipose triglyceride lipase (ATGL). Here, we identify fatty acid loading and nutrient deprivation-induced autophagy as stimuli of HILPDA-dependent lipid droplet growth. Using mouse embryonic fibroblasts and human tumor cells, we found that genetic ablation of HILPDA compromised hypoxia-fatty acid- and starvation-induced lipid droplet formation and triglyceride storage. Nutrient deprivation upregulated HILPDA protein posttranscriptionally by a mechanism requiring autophagic flux and lipid droplet turnover, independent of HIF1 transactivation. Mechanistically, loss of HILPDA led to elevated lipolysis, which could be corrected by inhibition of ATGL. Lipidomic analysis revealed not only quantitative but also qualitative differences in the glycerolipid and phospholipid profile of HILPDA wild-type and knockout cells, indicating additional HILPDA functions affecting lipid metabolism. Deletion studies of HILPDA mutants identified the N-terminal hydrophobic domain as sufficient for targeting to lipid droplets and restoration of triglyceride storage.
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Registered trials
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