ArticleAmerican journal of respiratory cell and molecular biology2015
Tuberous sclerosis complex 2 loss increases lysophosphatidylcholine synthesis in lymphangioleiomyomatosis.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Emerging Concepts in Pathogenesis, Multiomics Applications, and Clinical Research in Lymphangioleiomyomatosis.Seminars in respiratory and critical care medicine · 2025Review
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- The development for emerging biomarkers of lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2024Review
- "Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.Cancer communications (London, England) · 2024Review
- Upregulation of acid ceramidase contributes to tumor progression in tuberous sclerosis complex.JCI insight · 2023Article
- Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.Biomedicines · 2023Review
- Dysregulated lipid metabolism in lymphangioleiomyomatosis pathogenesis as a paradigm of chronic lung diseases.Frontiers in medicine · 2023Review
- Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment.Nature communications · 2022Article
- Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury.JCI insight · 2021Article
- Therapeutic Targeting of DGKA-Mediated Macropinocytosis Leads to Phospholipid Reprogramming in Tuberous Sclerosis Complex.Cancer research · 2021Article
- Therapeutic Targeting of the Secreted Lysophospholipase D Autotaxin Suppresses Tuberous Sclerosis Complex-Associated Tumorigenesis.Cancer research · 2020Article
- REDD1 loss reprograms lipid metabolism to drive progression ofGenes & development · 2020Article
- Article
- Hemp seed/evening primrose oil affects expression of STAT3, IL-17, and FOXP3Research in pharmaceutical sciences · 2019Article
- [Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Renal disease in tuberous sclerosis complex: pathogenesis and therapy.Nature reviews. Nephrology · 2018Review
- Vps34-mediated macropinocytosis in Tuberous Sclerosis Complex 2-deficient cells supports tumorigenesis.Scientific reports · 2018Article
- Therapeutic Benefit of Autophagy Modulation in Pompe Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Lymphangioleiomyomatosis (LAM) is a destructive lung disease affecting women. LAM is caused by mutations in the tuberous sclerosis complex (TSC) genes. The TSC protein complex inhibits the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), which is a master regulator of cellular metabolism. Using mass spectrometry-based lipid profiling, we analyzed plasma from patients with LAM and discovered elevated levels of four lysophosphatidylcholine (LPC) species (C16:0, C18:0, C18:1, and C20:4) compared with those in healthy control women. To investigate whether these lipids are generated in a TSC2-dependent manner, we profiled in vitro preclinical models of TSC/LAM and found significant LPC accumulation in TSC2-deficient cells relative to TSC2-expressing control cells. These lysoglycerophospholipid changes occurred alongside changes in other phospholipid and neutral lipid species. Treatment with rapamycin or torin1 or down-regulation of sterol regulatory element-binding protein (SREBP), a lipogenic transcription factor, did not suppress LPC in TSC2-deficient cells. Inhibition of distinct isoforms of phospholipase A2 decreased the proliferation of TSC2-deficient cells. Collectively, these results demonstrate that TSC2-deficient cells have enhanced choline phospholipid metabolism and reveal a novel function of the TSC proteins in choline lysoglycerophospholipid metabolism, with implications for disease pathogenesis and targeted therapeutic strategies.
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