Functional and Genetic Analysis of Compensatory Responses Induced in Tumors Caused by Loss of Scribble (apical-basal polarity). Alyssa Lesko^1,2, Shilpi Verghese³, Indrayani Waghmare³, Madhuri Kango-Singh^3,4,5. 1) Department of Chemistry,University of Dayton, Dayton, OH; 2) Department of Mathematics, University of Dayton, Dayton, Oh; 3) Department of Biology, University of Dayton, Dayton, OH; 4) Pre-Medical Programs, University of Dayton, Dayton OH; 5) Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton OH.

   The Hippo pathway has recently been identified to regulate the proliferation and survival of cells. scribble (scrib) is a tumor suppressor gene that is involved in cell polarity. There is evidence that cell death induction in the scrib mutant cells is correlated to an increase in Jun N-terminal Kinase (JNK) signaling due to activation of cell competition. However, increased survival of scrib mutant cells (by activation of P35 or in Minute background) leads to growth of massive tumors. My project will investigate how changes in Hippo signaling are important to cell-cell interactions regulated by scrib in different mutant conditions. Our previous work showed that JNK and Hippo pathway interact. scrib mutant cells showed increased levels of phospho-JNK compared to wild type and double mutant cells. We hypothesize that this interaction determines if tumor cells survive or are eliminated. To test this, I will look at the role of JNK when it is activated and down regulated in the Hippo pathway, as well as, its interaction with scrib. Our aims are: 1. Test the scrib-JNK interactions to assess role of JNK in scrib mediated overgrowth, and 2. Test the scrib-Hippo interactions to delineate the signaling interactions between scrib mutant cells and their neighbors to promote survival and over proliferation. Our findings from these studies will be presented.