Expanding the pathway

Alderton, Gemma

doi:10.1038/nrc2035

Research Highlight
Published: 16 November 2006

Tumour suppressors

Expanding the pathway

Gemma Alderton

Nature Reviews Cancer volume 6, page 903 (2006)Cite this article

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The Sav–Wts–Hpo pathway limits organ size by restricting cell growth and proliferation, and by activating apoptosis. Using D. melanogaster eye and wing discs as models for tissue growth, the groups showed that loss of the tumour suppressor Fat induces tissue overgrowth, unperturbed cell cycling and an inability to enter senescence. This phenotype is the same as that generated by the loss of Sav–Wts–Hpo signalling in these tissues, in part owing to the deregulated expression of the Sav–Wts–Hpo target gene cyclin E. Intriguingly, although the anti-apoptotic protein DIAP1 accumulates in fat mutant tissue, fat seems to be dispensable for developmental apoptosis. All three groups show that Fat is genetically and biochemically upstream of, and a positive regulator of, members of the Sav–Wts–Hpo signalling pathway.

Fat is a large transmembrane receptor, and the groups show that Fat functions upstream of Expanded (Ex), one of the upstream components of the Sav–Wts–Hpo pathway Fat is required for the stability and/or localization of Ex to the apical membrane of epithelial tissues. However, Fat was not required for the localization of Merlin, another upstream component, indicating that Merlin probably interacts with an alternative membrane-associated protein in a parallel pathway to Fat–Ex.

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ORIGINAL RESEARCH PAPERS

Bennett, F. C. & Harvey, K. F. Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signalling pathway. Curr. Biol. 12 Oct 2006 (doi:10.1016/j.cub.2006.09.045)
Silva, E., Tsatskis, Y., Gardano, L., Tapon, N., & McNeill, H. The tumour-suppressor gene fat controls tissue growth upstream of Expanded in the Hippo signalling pathway. Curr. Biol. 19 Sep 2006 (doi:10.1016/j.cub. 2006.09.004)
Willecke, M. et al. The Fat cadherin acts through the Hippo tumoursuppressor pathway to regulate tissue size. Curr. Biol. 19 Sep 2006 (doi:10.1016/j.cub.2006.09.005)

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