ArticleProceedings of the National Academy of Sciences of the United States of America2013
Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of Lymphangioleiomyomatosis on Diagnosis and Molecular Mechanism.BioMed research international · 2021Pooled it
- Current insight into the molecular mechanisms of lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2026Review
- MiT fusions, TSC1-TSC2 divergence, and stem-like programs reveal distinct origins and vulnerabilities in PEComa.Nature communications · 2026Article
- EIF4B Ser93 phosphorylation by ERK2 promotes epithelial-mesenchymal transition to drive colorectal cancer metastasis.Cell death & disease · 2026Article
- Machine Learning, Virtual Screening and Bioactivity Evaluation to Identify AJ-292/12941271 as an Anti-proliferative Agent and Target mTOR Protein.Current medicinal chemistry · 2026Article
- Synergistic effects of mTOR inhibitors with VEGFR3 inhibitors on the interaction between TSC2-mutated cells and lymphatic endothelial cells.Science China. Life sciences · 2025Article
- Increased malignancy risk in patients with lymphangioleiomyomatosis: findings from a Chinese cohort.Orphanet journal of rare diseases · 2025Article
- Targeting fibroblast-endothelial cell interactions in LAM pathogenesis using 3D spheroid models and spatial transcriptomics.JCI insight · 2025Article
- Transcriptomic analysis reveals the key role of inflammatory and immune signaling in the anti-perimenopausal depression effects of Bushen Shugan Huayu decoction.Frontiers in psychiatry · 2025Article
- Targeting Fibroblast-Endothelial Interactions in LAM Pathogenesis: 3D Spheroid and Spatial Transcriptomic Insights for Therapeutic Innovation.bioRxiv : the preprint server for biology · 2024Article
- Novel developments in the study of estrogen in the pathogenesis and therapeutic intervention of lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2024Review
- Lymphangioleiomyomatosis and pregnancy: a mini-review.Archives of gynecology and obstetrics · 2024Review
- PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis.Cancer research · 2024Article
- Upregulation of acid ceramidase contributes to tumor progression in tuberous sclerosis complex.JCI insight · 2023Article
- Risk of pneumothorax in Birt-Hogg-Dubé syndrome during pregnancy and birth.Frontiers in medicine · 2023Article
- Perivascular epithelioid cell tumor (PEComa) of the uterus: Challenges of pregnancy in determining prognosis and optimal treatment.Gynecologic oncology reports · 2022Article
- Sex-Steroid Signaling in Lung Diseases and Inflammation.Advances in experimental medicine and biology · 2021Article
- Single-Cell Transcriptomic Analysis Identifies a Unique Pulmonary Lymphangioleiomyomatosis Cell.American journal of respiratory and critical care medicine · 2020Article
- Cystic Interstitial Lung Diseases: A Pictorial Review and a Practical Guide for the Radiologist.Diagnostics (Basel, Switzerland) · 2020Review
- Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.Orphanet journal of rare diseases · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women associated with the metastasis of tuberin-null cells with hyperactive mammalian target of rapamycin complex 1 (mTORC1) activity. Clinical trials with the mTORC1 inhibitor rapamycin have revealed partial efficacy but are not curative. Pregnancy appears to exacerbate LAM, suggesting that estrogen (E2) may play a role in the unique features of LAM. Using a LAM patient-derived cell line (bearing biallelic Tuberin inactivation), we demonstrate that E2 stimulates a robust and biphasic activation of ERK2 and transcription of the late response-gene Fra1 associated with epithelial-to-mesenchymal transition. In a carefully orchestrated collaboration, activated mTORC1/S6K1 signaling enhances the efficiency of Fra1 translation of Fra1 mRNA transcribed by the E2-ERK2 pathway, through the phosphorylation of the S6K1-dependent eukaryotic translation initiation factor 4B. Our results indicate that targeting the E2-ERK pathway in combination with the mTORC1 pathway may be an effective combination therapy for LAM.
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