ArticleScientific reports2019
Rapalog resistance is associated with mesenchymal-type changes in Tsc2-null cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Inhibition of NAMPT as a therapeutic strategy to suppress tumor growth in lymphangioleiomyomatosis.Biochimica et biophysica acta. Molecular cell research · 2025Article
- Tyrosine Kinase Inhibitors Diminish Renal Neoplasms in a Tuberous Sclerosis Model Via Induction of Apoptosis.Molecular cancer therapeutics · 2023Article
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- Exosome Release by Glucose Deprivation Is Important for the Viability of TSC-Null Cells.Cells · 2022Article
- LAM Cells as Potential Drivers of Senescence in Lymphangioleiomyomatosis Microenvironment.International journal of molecular sciences · 2022Article
- Long non-coding RNA ACTA2-AS1 inhibits the cisplatin resistance of non-small cell lung cancer cells through inhibiting autophagy by suppressing TSC2.Cell cycle (Georgetown, Tex.) · 2022Article
- Chemical Biology Screening Identifies a Vulnerability to Checkpoint Kinase Inhibitors in TSC2-Deficient Renal Angiomyolipomas.Frontiers in oncology · 2022Article
- Raising the Flag for Mast Cells as a Novel Target in Lymphangioleiomyomatosis.American journal of respiratory and critical care medicine · 2021Article
- CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis.International journal of molecular sciences · 2021Review
- Inhibition of the mechanistic target of rapamycin induces cell survival via MAPK in tuberous sclerosis complex.Orphanet journal of rare diseases · 2020Article
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- Possible Novel Therapeutic Targets in Lymphangioleiomyomatosis Treatment.Frontiers in medicine · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) are caused by inactivating mutations in TSC1 or TSC2, leading to mTORC1 hyperactivation. The mTORC1 inhibitors rapamycin and analogs (rapalogs) are approved for treating of TSC and LAM. Due to their cytostatic and not cytocidal action, discontinuation of treatment leads to tumor regrowth and decline in pulmonary function. Therefore, life-long rapalog treatment is proposed for the control of TSC and LAM lesions, which increases the chances for the development of acquired drug resistance. Understanding the signaling perturbations leading to rapalog resistance is critical for the development of better therapeutic strategies. We developed the first Tsc2-null rapamycin-resistant cell line, ELT3-245, which is highly tumorigenic in mice, and refractory to rapamycin treatment. In vitro ELT3-245 cells exhibit enhanced anchorage-independent cell survival, resistance to anoikis, and loss of epithelial markers. A key alteration in ELT3-245 is increased β-catenin signaling. We propose that a subset of cells in TSC and LAM lesions have additional signaling aberrations, thus possess the potential to become resistant to rapalogs. Alternatively, when challenged with rapalogs TSC-null cells are reprogrammed to express mesenchymal-like markers. These signaling changes could be further exploited to induce clinically-relevant long-term remissions.
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Registered trials
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