Organisms must tightly regulate cell proliferation and cell death to generate organs with stereotypic size, shape, and function. A cohesive appreciation of the underlying mechanisms and how they are deregulated in cancers remain elusive. Addressing these knowledge gaps will broaden our understanding of epithelial biology and potentially expose novel therapeutic targets.  

The first part of the talk focuses on hedgehog (Hh) and hippo, two central and broadly conserved growth signals. Hh and Hippo cooperate to drive tissue growth in flies and vertebrates. The mechanisms for countering Hh and hippo to prevent tissue overgrowth are not well understood. Using Drosophila, we found that the small G-protein ARF6 promotes Hh cell-cell signaling, which is required for hippo-mediated tissue growth. The JNK-interacting protein JIP3/Syd balances hippo-mediated tissue growth by inhibiting the anti-apoptotic molecule Diap1, thereby promoting cell death in tissues and achieving size stereotypy.   

The second part of the talk will highlight the role of signaling extracellular vesicles (EV) in tissue homeostasis and the opportunity they present for cancer diagnostics. We will discuss our recent findings suggesting that oncogenic EGFR/RAS usurp EV and other mechanisms to establish drug-resistance and promote tumor overgrowth.