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Article
The Fat Cadherin Acts through the Hippo Tumor-Suppressor Pathway to Regulate Tissue Size
Current Biology
  • Maria Willecke, University of Texas M.D. Anderson Cancer Center
  • Fisun Hamaratoglu, University of Texas M.D. Anderson Cancer Center
  • Madhuri Kango-Singh, University of Dayton
  • Ryan Udan, University of Texas M.D. Anderson Cancer Center
  • Chiao-lin Chen, University of Texas M.D. Anderson Cancer Center
  • Chunyao Tao, University of Texas M.D. Anderson Cancer Center
  • Xinwei Zhang, University of Texas M.D. Anderson Cancer Center
  • Georg Halder, University of Texas M.D. Anderson Cancer Center
Document Type
Article
Publication Date
11-1-2006
Abstract

Background: The Hippo tumor-suppressor pathway has emerged as a key signaling pathway that controls tissue size in Drosophila. Merlin, the Drosophila homolog of the human Neurofibromatosis type-2 (NF2) tumor-suppressor gene, and the related protein Expanded are the most upstream components of the Hippo pathway identified so far. However, components acting upstream of Expanded and Merlin, such as transmembrane receptors, have not yet been identified.

Results: Here, we report that the protocadherin Fat acts as an upstream component in the Hippo pathway. Fat is a known tumor-suppressor gene in Drosophila, and fat mutants have severely overgrown imaginal discs. We found that the overgrowth phenotypes of fatmutants are similar to those of mutants in Hippo pathway components: fat mutant cells continued to proliferate after wild-type cells stopped proliferating, and fat mutant cells deregulated Hippo target genes such as cyclin E and diap1. Fat acts genetically and biochemically upstream of other Hippo pathway components such as Expanded, the Hippo and Warts kinases, and the transcriptional coactivator Yorkie. Fat is required for the stability of Expanded and its localization to the plasma membrane. In contrast, Fat is not required for Merlin localization, and Fat and Merlin act in parallel in growth regulation.

Conclusions: Taken together, our data identify a cell-surface molecule that may act as a receptor of the Hippo signaling pathway.

ISBN/ISSN
0960-9822
Document Version
Published Version
Comments

This article is available in the repository through the publication's open archive. Permission documentation is on file.

Publisher
Elsevier
Peer Reviewed
Yes
Citation Information
Maria Willecke, Fisun Hamaratoglu, Madhuri Kango-Singh, Ryan Udan, et al.. "The Fat Cadherin Acts through the Hippo Tumor-Suppressor Pathway to Regulate Tissue Size" Current Biology Vol. 16 Iss. 21 (2006)
Available at: http://works.bepress.com/madhuri_kango-singh/2/