Title |
Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3
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Published in |
eLife, July 2017
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DOI | 10.7554/elife.23202 |
Pubmed ID | |
Authors |
Peter J Klover, Rajesh L Thangapazham, Jiro Kato, Ji-an Wang, Stasia A Anderson, Victoria Hoffmann, Wendy K Steagall, Shaowei Li, Elizabeth McCart, Neera Nathan, Joshua D Bernstock, Matthew D Wilkerson, Clifton L Dalgard, Joel Moss, Thomas N Darling |
Abstract |
Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKO(Prrx1-cre) mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database. Signature component Lgals3 encoding galectin-3 was increased in Tsc2-deficient cells and serum of Tsc2cKO(Prrx1)-cre mice. Galectin-3 was increased in TSC-related skin tumors, angiomyolipomas, and lymphangioleiomyomatosis with serum levels in patients with lymphangioleiomyomatosis correlating with impaired lung function and angiomyolipoma presence. Our results demonstrate Tsc2-deficient mesenchymal progenitors cause aberrant morphogenic signals, and identify an expression signature including Lgals3 relevant for human disease of TSC1/TSC2 inactivation and mTORC1 hyperactivity. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 5 | 50% |
United Kingdom | 2 | 20% |
France | 1 | 10% |
Unknown | 2 | 20% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 40% |
Practitioners (doctors, other healthcare professionals) | 3 | 30% |
Scientists | 3 | 30% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 35 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 6 | 17% |
Student > Master | 5 | 14% |
Researcher | 4 | 11% |
Student > Bachelor | 3 | 9% |
Student > Postgraduate | 3 | 9% |
Other | 7 | 20% |
Unknown | 7 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 9 | 26% |
Biochemistry, Genetics and Molecular Biology | 6 | 17% |
Agricultural and Biological Sciences | 4 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 9% |
Chemistry | 2 | 6% |
Other | 3 | 9% |
Unknown | 8 | 23% |