ArticleCancer research2016
Mesenchymal Tumorigenesis Driven by TSC2 Haploinsufficiency Requires HMGA2 and Is Independent of mTOR Pathway Activation.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Neural crest cell signatures drive tumorigenesis in tuberous sclerosis complex and lymphangioleiomyomatosis.JCI insight · 2026Article
- Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.The Journal of clinical investigation · 2023Article
- Tyrosine Kinase Inhibitors Diminish Renal Neoplasms in a Tuberous Sclerosis Model Via Induction of Apoptosis.Molecular cancer therapeutics · 2023Article
- Raising the Flag for Mast Cells as a Novel Target in Lymphangioleiomyomatosis.American journal of respiratory and critical care medicine · 2021Article
- Article
- High Mobility Group AT-Hook 2 (HMGA2) Oncogenicity in Mesenchymal and Epithelial Neoplasia.International journal of molecular sciences · 2020Review
- Inactivation ofAmerican journal of physiology. Renal physiology · 2019Article
- Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse.Scientific reports · 2019Article
- A genome-wide Drosophila epithelial tumorigenesis screen identifies Tetraspanin 29Fb as an evolutionarily conserved suppressor of Ras-driven cancer.PLoS genetics · 2018Article
- Rapamycin-independent IGF2 expression in Tsc2-null mouse embryo fibroblasts and human lymphangioleiomyomatosis cells.PloS one · 2018Article
- Melanocyte Stem Cell Activation and Translocation Initiate Cutaneous Melanoma in Response to UV Exposure.Cell stem cell · 2017Article
- Reprogramming patient-derived tumor cells generates model cell lines for tuberous sclerosis-associated lymphangioleiomyomatosis.Oncoscience · 2017Article
- Human Pluripotent Stem Cell-DerivedCancer research · 2017Article
- Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.Cancer science · 2017Review
- Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.Biochimica et biophysica acta · 2016Review
- A panel of four genes accurately differentiates benign from malignant thyroid nodules.Journal of experimental & clinical cancer research : CR · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberous sclerosis (TSC) is a tumor suppressor gene syndrome that is associated with the widespread development of mesenchymal tumor types. Genetically, TSC is said to occur through a classical biallelic inactivation of either TSC genes (TSC1, hamartin or TSC2, tuberin), an event that is implicated in the induction of the mTOR pathway and subsequent tumorigenesis. High Mobility Group A2 (HMGA2), an architectural transcription factor, is known to regulate mesenchymal differentiation and drive mesenchymal tumorigenesis in vivo. Here, we investigated the role of HMGA2 in the pathogenesis of TSC using the TSC2(+/-) mouse model that similarly mirrors human disease and human tumor samples. We show that HMGA2 expression was detected in 100% of human and mouse TSC tumors and that HMGA2 activation was required for TSC mesenchymal tumorigenesis in genetically engineered mouse models. In contrast to the current dogma, the mTOR pathway was not activated in all TSC2(+/-) tumors and was elevated in only 50% of human mesenchymal tumors. Moreover, except for a subset of kidney tumors, tuberin was expressed in both human and mouse tumors. Therefore, haploinsufficiency of one TSC tumor suppressor gene was required for tumor initiation, but further tumorigenesis did not require the second hit, as previously postulated. Collectively, these findings demonstrate that tissue-specific genetic mechanisms are employed to promote tumor pathogenesis in TSC and identify a novel, critical pathway for potential therapeutic targeting.
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