ArticleThe Journal of experimental medicine2014
Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- Novel treatment strategies for lymphangioleiomyomatosis: a narrative review.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- The development for emerging biomarkers of lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2024Review
- Plasmacytoid Dendritic Cells Mediate CpG-ODN-induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- Case Report: Patent ductus arteriosus with tuberous sclerosis complex.Frontiers in cardiovascular medicine · 2024Article
- Upregulation of acid ceramidase contributes to tumor progression in tuberous sclerosis complex.JCI insight · 2023Article
- Targeting SPHK1/S1PR3-regulated S-1-P metabolic disorder triggers autophagic cell death in pulmonary lymphangiomyomatosis (LAM).Cell death & disease · 2022Article
- RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1.Molecular therapy oncolytics · 2021Article
- MITF is a driver oncogene and potential therapeutic target in kidney angiomyolipoma tumors through transcriptional regulation of CYR61.Oncogene · 2021Article
- Single-Cell Transcriptomic Analysis Identifies a Unique Pulmonary Lymphangioleiomyomatosis Cell.American journal of respiratory and critical care medicine · 2020Article
- Inhibition of the mechanistic target of rapamycin induces cell survival via MAPK in tuberous sclerosis complex.Orphanet journal of rare diseases · 2020Article
- Article
- Tumors with TSC mutations are sensitive to CDK7 inhibition through NRF2 and glutathione depletion.The Journal of experimental medicine · 2019Article
- A study of sirolimus and mTOR kinase inhibitor in a hypomorphicAmerican journal of physiology. Renal physiology · 2019Article
- Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis.JCI insight · 2019Article
- Review
- Renal disease in tuberous sclerosis complex: pathogenesis and therapy.Nature reviews. Nephrology · 2018Review
- Systems biology approach reveals a link between mTORC1 and G2/M DNA damage checkpoint recovery.Nature communications · 2018Article
- The Lymphangioleiomyomatosis Lung Cell and Its Human Cell Models.American journal of respiratory cell and molecular biology · 2018Review
- Reply to Yanagisawa: Treatment of Pulmonary Lymphangioleiomyomatosis during Pregnancy.American journal of respiratory and critical care medicine · 2018Article
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
Lymphangioleiomyomatosis (LAM) is a progressive neoplastic disorder that leads to lung destruction and respiratory failure primarily in women. LAM is typically caused by tuberous sclerosis complex 2 (TSC2) mutations resulting in mTORC1 activation in proliferative smooth muscle-like cells in the lung. The female predominance of LAM suggests that estradiol contributes to disease development. Metabolomic profiling identified an estradiol-enhanced prostaglandin biosynthesis signature in Tsc2-deficient (TSC(-)) cells, both in vitro and in vivo. Estradiol increased the expression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin biosynthesis, which was also increased at baseline in TSC-deficient cells and was not affected by rapamycin treatment. However, both Torin 1 treatment and Rictor knockdown led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin production was also increased in TSC-deficient cells. In preclinical models, both Celecoxib and aspirin reduced tumor development. LAM patients had significantly higher serum prostaglandin levels than healthy women. 15-epi-lipoxin-A4 was identified in exhaled breath condensate from LAM subjects and was increased by aspirin treatment, indicative of functional COX-2 expression in the LAM airway. In vitro, 15-epi-lipoxin-A4 reduced the proliferation of LAM patient-derived cells in a dose-dependent manner. Targeting COX-2 and prostaglandin pathways may have therapeutic value in LAM and TSC-related diseases, and possibly in other conditions associated with mTOR hyperactivation.
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