Abstract A22: Mechanisms of oncogenic cooperation between EGFR/Ras and Hippo pathways in Drosophila and human cellular transformation models

Abstract

Abstract The hippo/Salvador kinase cascade is a highly conserved signaling pathway regulating growth and organ size from Drosophila to mammals. The invertebrate-specific microRNA, bantam, is a key target and effector downstream of the Drosophila hippo pathway. Bantam inhibits the pro-apoptotic factor hid and promotes growth through an as yet unidentified mechanism. The EGFR/Ras pathway coordinates growth and patterning in Drosophila. We characterize a molecular circuit involving bantam, socs36E and EGFR that regulates tissue growth. Socs36E is a direct bantam target that negatively regulates wing size. Socs36E buffers EGFR activity by acting in a negative feedback loop with EGFR. Interestingly, bantam and socs36E repress each other forming a potential bistable switch. This switch might allow effective repression of socs36E during the rapid growth phase of wing disc development. Therefore, bantam represents a unique molecular linkage connecting hippo and EGFR signaling in promoting growth. Furthermore, we found that the mammalian socs family members SOCS5 and SOCS6 are targeted by an oncogenic miRNA, which plays a role in RasV12 mediated tumoriogenesis in soft agar assays. Therefore, the SOCS family proteins are evolutionarily conserved regulators of growth and cancer transformation. Citation Format: Xin Hong, Stephen Michael Cohen. Mechanisms of oncogenic cooperation between EGFR/Ras and Hippo pathways in Drosophila and human cellular transformation models. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A22.