Lgl, the SWH pathway and tumorigenesis: It's a matter of context & competition!

Cell Cycle. 2010 Aug 15;9(16):3202-12. doi: 10.4161/cc.9.16.12633. Epub 2010 Aug 10.

Abstract

Loss of function of the neoplastic tumors suppressors, lgl, scrib and dlg or overexpression of the apical polarity components, Crumbs and atypical protein kinase C (aPKC), are associated with polarity loss and tissue overgrowth, however, the mechanism behind these effects is poorly understood. In our recent study, we showed that Lgl, aPKC and Crumbs mediate their effects on proliferation and survival via the Salvador/Warts/Hippo (SWH) tumor suppressor pathway. Loss of lgl can lead to substantial overgrowth, however the lgl mutant phenotype can be quite variable and the amount of overgrowth of the mutant tissue, its survival and ultimate fate is strongly determined by context and competition. In this extra-view we present a more detailed description of the lgl mutant phenotype and highlight the phenotypic differences between lgl and SWH pathway mutant phenotypes. In addition, we explore the role for the Jun kinase (JNK) pathway in the development of the lgl mutant phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Proteins / metabolism*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Kinase 4 / metabolism
  • Membrane Proteins / metabolism
  • Mutation
  • Neoplasms / etiology
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / physiology

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Scrib protein, Drosophila
  • Tumor Suppressor Proteins
  • crb protein, Drosophila
  • l(2)gl protein, Drosophila
  • sav protein, Drosophila
  • dlg1 protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila
  • MAP Kinase Kinase 4