Lgl, the SWH pathway and tumorigenesis: It's a matter of context & competition!
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.
Grzeschik
Nicola A
NA
Cell Cycle and Development Lab, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia. nico.grzeschik@petermac.org
Parsons
Linda M
LM
Richardson
Helena E
HE
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000209:etiology; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000099317:Hippo Kinases
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D048670:MAP Kinase Kinase 4; D008565:Membrane Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C404683:Scrib protein, Drosophila; C064360:crb protein, Drosophila; C081435:l(2)gl protein, Drosophila; C465504:sav protein, Drosophila; C070350:dlg1 protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases