ArticlePLoS genetics2017
Epistatic interaction between the lipase-encoding genes Pnpla2 and Lipe causes liposarcoma in mice.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Lipolysis in Health and Disease: Pathways, Regulation, and Metabolic Consequences.Current diabetes reports · 2026Review
- Impact of sleep deprivation on colon cancer: Unraveling the KynA-P4HA2-HIF-1α axis in tumor lipid metabolism and metastasis.Molecular metabolism · 2025Article
- Three-dimensional models: from cell culture to Patient-Derived Organoid and its application to future liposarcoma research.Oncology research · 2025Review
- Inhibitory Activity ofJournal of microbiology and biotechnology · 2024Article
- Comprehensive Analysis of a Six-Gene Signature Predicting Survival and Immune Infiltration of Liposarcoma Patients and Deciphering Its Therapeutic Significance.International journal of molecular sciences · 2024Article
- ATGL promotes colorectal cancer growth by regulating autophagy process and SIRT1 expression.Medical oncology (Northwood, London, England) · 2023Article
- Cooperative lipolytic control of neuronal triacylglycerol by spastic paraplegia-associated enzyme DDHD2 and ATGL.Journal of lipid research · 2023Article
- G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells.Translational oncology · 2023Article
- Exosome-Based Liquid Biopsy Approaches in Bone and Soft Tissue Sarcomas: Review of the Literature, Prospectives, and Hopes for Clinical Application.International journal of molecular sciences · 2023Review
- The p53 tumor suppressor regulates AKR1B1 expression, a metastasis-promoting gene in breast cancer.Frontiers in molecular biosciences · 2023Article
- Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review.Frontiers in endocrinology · 2022Review
- Recent Advances on the Role of ATGL in Cancer.Frontiers in oncology · 2022Review
- Review
- Article
- Adipose triglyceride lipase promotes the proliferation of colorectal cancer cells via enhancing the lipolytic pathway.Journal of cellular and molecular medicine · 2021Article
- Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation.BioMed research international · 2021Article
- Hypoxia, hypoxia-inducible gene 2 (HIG2)/HILPDA, and intracellular lipolysis in cancer.Cancer letters · 2020Review
- Adipose triglyceride lipase activity regulates cancer cell proliferation via AMP-kinase and mTOR signaling.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Article
- Accurate 3-gene-signature for early diagnosis of liposarcoma progression.Clinical sarcoma research · 2020Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Liposarcoma is an often fatal cancer of fat cells. Mechanisms of liposarcoma development are incompletely understood. The cleavage of fatty acids from acylglycerols (lipolysis) has been implicated in cancer. We generated mice with adipose tissue deficiency of two major enzymes of lipolysis, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), encoded respectively by Pnpla2 and Lipe. Adipocytes from double adipose knockout (DAKO) mice, deficient in both ATGL and HSL, showed near-complete deficiency of lipolysis. All DAKO mice developed liposarcoma between 11 and 14 months of age. No tumors occurred in single knockout or control mice. The transcriptome of DAKO adipose tissue showed marked differences from single knockout and normal controls as early as 3 months. Gpnmb and G0s2 were among the most highly dysregulated genes in premalignant and malignant DAKO adipose tissue, suggesting a potential utility as early markers of the disease. Similar changes of GPNMB and G0S2 expression were present in a human liposarcoma database. These results show that a previously-unknown, fully penetrant epistatic interaction between Pnpla2 and Lipe can cause liposarcoma in mice. DAKO mice provide a promising model for studying early premalignant changes that lead to late-onset malignant disease.
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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.