Tuberous sclerosis complex (TSC) is a rare genetic disorder associated with benign tumour formation. The disease is caused by loss-of-function mutations in either of the tumour suppressor genes TSC1 or TSC2. In normal cells, the proteins encoded by these genes collectively inhibit mTORC1 (mechanistic target of rapamycin complex I) signalling; when absent, mTORC1 signalling is increased. Paradoxically, in other disorders characterised by augmented mTORC1 signalling, overt malignancies are observed. Ess and colleagues exploited this difference to gain mechanistic insights into tumorigenesis. They established a zebrafish model of TSC that develops cancer, by generating tsc2;p53 compound mutants. Compared with p53 single mutants, tumorigenesis and angiogenesis were enhanced in tsc2;p53 zebrafish. Treatment with an mTORC1 inhibitor, rapamycin, inhibited tumour formation. This work provides in vivo evidence that cancer risk in p53-deficient individuals might be modulated by TSC1 or TSC2 mutations. Page 925
Insights into cancer risk from a tuberous sclerosis complex zebrafish model
Insights into cancer risk from a tuberous sclerosis complex zebrafish model. Dis Model Mech 1 July 2013; 6 (4): 867. doi:
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DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens
The abstract submission deadline for our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ is 14 July 2023. Find out more and register here.
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In our recent editor’s choice, Liqin Zhu and colleagues describe how they used in vitro liver spheroid models consisting of both parenchymal and non-parenchymal cells to reveal a hepatoprotective role for peritumoral hepatic stellate cells in liver tumorigenesis.
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Thousands of genomic loci have been linked to hematopoietic traits and diseases, yet many await functional validation. Michael Gundry and Vijay G. Sankaran discuss recent advances in genome editing and the challenges associated with using these techniques to assess variant function in primary hematopoietic cells.
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