External seminar - Caroline Dillard

Caroline DILLARD

ROLE AND REGULATION OF NF-kB - DRIVEN TUMORIGENESIS

 

Seminal studies in flies and later mammals established that NF-kB transcription factors direct development and are master regulators of inflammation and innate immunity. Additionally, there is extensive evidence that NF-kB is active in mammalian cancer cell lines where it promotes survival, proliferation, epithelial-to-mesenchymal transition (EMT), invasion, angiogenesis and metabolic reprogramming. In flies, NF-kBs have been implicated in the phenomenon of cell competition where NF-kB drive Hid or Rpr-driven cell death in losing neighbouring cells adjacent to either Myc high, or Yki high (Fat-/-) hyperplastic cells. However, evidence for cell-autonomous functions of NF-kBs in tumorigenesis is lacking. Using a Drosophila melanogaster carcinoma model, we identified an inflammation signature in the tumor cell population. Functional screening identified NF-kB/Dorsal as being required for growth of RasV12, scribRNAi tumors. Here we describe the activation, regulation and downstream functions of Dorsal in growth and invasion in this model, extending the similarities of NF-kB functions between mammals and flies to also apply to tumorigenesis.