722A Poster - 11. Cell division and cell growth
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
arushi rai ¹; Indrayani Waghmare ³; Amit Singh ^1,2; Madhuri Kango-Singh ^1,2

Affiliations:
1) Department of Biology, University of Dayton, Dayton, OH; 2) Integrative Science and Engineering Center, University of Dayton, Dayton, OH; 3) Department of Cell and Developmental Biology Vanderbilt University, Nashville, TN

Keywords:
r. tumor suppressors and oncogenes; r. tumor suppressors and oncogenes

Studies in Drosophila and other tumor models have revealed cancer promoting signaling interactions and transcriptional addictions in tumors cells. The Hippo pathway effector, Yorkie (Yki) is a key mediator of such interactions, and presents an attractive opportunity to study transcriptional dependencies in cancer cells. The Ras^V12, scrib^-/- tumor mosaic model is well-established and shows activation of oncogenic Ras in the background of impaired apical-basal polarity. This model is widely used study molecular mechanisms and signaling events downstream of the oncogenic Ras and Ras-mediated Yorkie (Yki) activation in Ras^V12, scrib^-/- tumor cells. Previously, we have shown that in Ras^V12, scrib^-/- cells Wingless (Wg), Caspases (e.g., the initiator caspase Dronc) and JNK are activated to promote tumorigenesis through their non-apoptotic roles. Amongst these, Wg/Wnt pathway is known to act via canonical and non-canonical pathways during development and cancer, and interact with Yki to promote cancer growth. Genetic epistasis showed that Wg acts upstream of Caspases, JNK and Yki, and downregulation of Wg reduced tumor growth by downregulation of Caspases, JNK and Yki reporters. Our goal is to further understand how the two evolutionarily conserved signaling pathways i.e., Hippo and Wingless crosstalk and interact with each other to regulate tumor growth. To understand this intricate wiring of Wingless-Yorkie during tumor growth and invasion, we will use the Ras^V12, scrib^-/- tumor model in Drosophila imaginal discs. Preliminary data showed that wg transcriptional reporters are upregulated in Ras^V12, scrib^-/- cells, suggesting that increased accumulation of Wg may be due to increased transcription. In other contexts, wg is shown as a transcriptional target of Yki. Therefore, we will test for (a) the effects of Yorkie protein, the main effector molecule of Hippo pathway, on wg transcription and expression of other Wg pathway components by reporter assays, and qRT-PCR-based approaches, and (b) feedback interactions that promote tumorigenesis using genetic epistasis-, and immunohistochemistry-based approaches. Here, we present our progress on the organization of the molecular network involving Wingless and Yorkie.