Editors' ChoiceDevelopment

Hippo Pathway Gains Fat

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Science's STKE  14 Nov 2006:
Vol. 2006, Issue 361, pp. tw389
DOI: 10.1126/stke.3612006tw389

Three papers this week connect the atypical cadherin Fat to the Hippo signaling pathway (Hippo is a serine-threonine kinase that resembles the yeast Sterile-20 protein and acts as a tumor suppressor in Drosophila), which is implicated in the control of tissue or organ size. Fat is also a tumor suppressor in flies, and fat mutant flies showed overgrown imaginal discs similar to those of flies with mutations in the Hippo pathway. Cells lacking Fat grew and proliferated more quickly than did control cells and had increased amounts of Cyclin E and of the antiapoptotic protein Diap1. In the planar-cell polarity pathway, Fat interacts with another atypical cadherin, and the two are thought to function as receptor and ligand, respectively. In the control of organ size analyzed here, Fat appeared to interact with the cytoskeletal adaptor protein known as Expanded, which is the most upstream protein previously shown to function in the Hippo pathway. Fat was required for stability of the Expanded protein and its normal localization at the plasma membrane at apical junctions. The results indicate that Fat may serve as a cell-surface scaffold or receptor that leads to activation of the Hippo pathway through a mechanism that remains to be fully understood. The components of the Hippo pathway are conserved in vertebrates, and some have been implicated in tumorigenesis, but their roles in a pathway controlling cell proliferation or organ size remain to be investigated.

M. Willecke, F. Hamaratoglu, M. Kango-Singh, R. Udan, C.-L. Chen, C. Tao, X. Zhang, G. Halder, The Fat cadherin acts through the Hippo tumor-suppressor pathway to regulate tissue size. Curr. Biol. 16, 2090-2100 (2006). [PubMed]

F. C. Bennett, K. F. Harvey, Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr. Biol. 16, 2101-2110 (2006). [PubMed]

E. Silva, Y. Tsatskis, L. Gardano, N. Tapon, H. McNeill, The tumor-suppressor gene fat controls tissue growth upstream of Expanded in the Hippo signaling pathway. Curr. Biol. 16, 2081-2089 (2006). [PubMed]

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