Different roles of dFOXO and HSF in spatio-temporal dynamics of stress-inducible Hsp70 in lgl-yorkie & lgl-Ras driven epithelial tumours inDrosophila

Abstract

AbstractOncogenic cells recruit diverse cellular survival machineries, including the highly conserved heat shock proteins (Hsps), to counter stressful conditions during tumour progression. Despite important roles of Hsps in several cancers, poor understanding of their regulation leaves major gaps in identifying mechanisms of cellular stress responses exploited by cancer cells. Following our earlier report of stress inducible Hsp70 expression only in a few cells in polarity defective tumorous clones, we now show that Hsp70 is expressed only in neoplastic tumours. Hsp70’s expression at 72h after clone induction is mostly limited to a fewlgl-ykiOEcells exhibiting mesenchymal features in hypoxic zone closer to tracheae, although all tumorous cells expresshsp70transcripts. Down-regulation of thehsp70abut nothsp70bcluster transcripts substantially suppresses growth oflgl-ykiOEclones without affecting their early establishment. However, over-expression of Hsp70 or Hsp70-cochaperone DnaJ suppresslgl-ykiOEclones’ growth at early stage. This spatially and temporally regulated expression of Hsp70 inlgl-ykiOEclones is independent of HSF but requires dFOXO and JNK signalling, while a nearly similar pattern of Hsp70 expression inlgl-RasV12clones requires HSF, rather than dFOXO. Such context dependent Hsp70 regulation provides novel insight into stress regulatory machinery in cancer cells.