TY - JOUR TI - Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3 AU - Klover, Peter J AU - Thangapazham, Rajesh L AU - Kato, Jiro AU - Wang, Ji-an AU - Anderson, Stasia A AU - Hoffmann, Victoria AU - Steagall, Wendy K AU - Li, Shaowei AU - McCart, Elizabeth AU - Nathan, Neera AU - Bernstock, Joshua D AU - Wilkerson, Matthew D AU - Dalgard, Clifton L AU - Moss, Joel AU - Darling, Thomas N A2 - Pan, Duojia VL - 6 PY - 2017 DA - 2017/07/11 SP - e23202 C1 - eLife 2017;6:e23202 DO - 10.7554/eLife.23202 UR - https://doi.org/10.7554/eLife.23202 AB - 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. Tsc2cKOPrrx1-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 Tsc2cKOPrrx1-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. KW - galectin-3 KW - tuberous sclerosis complex KW - mTORC1 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -