Deciphering tumor-suppressor signaling in flies: genetic link between Scribble/Dlg/Lgl and the Hippo pathways.
Loss of apico-basal polarity is one of the crucial factors that drives epithelial tumor progression. scribble/discs large/lethal giant larvae (scrib/dlg/lgl), a group of apico-basal polarity genes, were initially identified as members of "neoplastic" tumor-suppressors in flies. The components of the Hippo signaling pathway, which is crucial for organ size control and cancer development, were also identified through Drosophila genetic screens as members of "hyperplastic" tumor-suppressors. Accumulating evidence in recent studies implies that these two tumor-suppressor signaling pathways are not mutually exclusive but rather cooperatively act to give rise to highly malignant tumors. The interaction of these tumor-suppressor pathways could include deregulations of actin cytoskeleton, cell-cell contact, and apical-domain size of the epithelial cell.
Department of Cell Biology, G-COE, Kobe University Graduate School of Medicine, Chuo-ku, Japan.
Masato
M
Enomoto
Tatsushi
T
Igaki
D000199:Actins / Q000235:genetics; D000818:Animals; D016764:Cell Polarity / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000099317:Hippo Kinases
D000199:Actins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C404683:Scrib protein, Drosophila; C081435:l(2)gl protein, Drosophila; C070350:dlg1 protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases