Drosophila endocytic neoplastic tumor suppressor genes regulate Sav/Wts/Hpo signaling and the c-Jun N-terminal kinase pathway.

摘要: Genetic screens in the fruit fly Drosophila melanogaster have identified a class of neoplastic tumor suppressor genes (endocytic nTSGs) that encode proteins localize to endosomes and facilitate trafficking membrane-bound receptors adhesion molecules into degradative lysosome. Loss endocytic nTSGs transforms imaginal disc epithelia highly proliferative, invasive tissues fail differentiate display defects cellular apicobasal polarity, tissue architecture. As vertebrate homologs some are linked formation, identifying molecular changes signaling associated with nTSG loss could inform understanding transformation vertebrates. Here, we show mutations act at multiple steps endolysosomal pathway lead autonomous activation Sav/Wts/Hpo (SWH) transcriptional effector Yki (YAP/TAZ vertebrates) Jun N-terminal kinase (JNK), which is known promote activity cells disrupted polarity. JNK elevated by pathway, including AP-2σ gene, encodes component AP-2 adaptor complex recruits cargoes clathrin-coated pits for subsequent internalization. Moreover, reduction can decrease caused altered endocytosis. These studies reveal broad requirement components regulating SWH outputs place network involves two major pathways implicated oncogenesis.