Drosophila CRC models to study tumor-promoting signaling interactions

Drosophila CRC models to study tumor-promoting signaling interactions

Presenter(s)

Venolia Adjei, Sydney Anderson, Brandon Clark, Maria El Biri, Evelyn Krebs, Edmund O'Rourke, Arushi Rai, Olivia Stolly, Kate Weber

Comments

3:00-4:15, Kennedy Union Ballroom

Description

Colorectal cancer (CRC) is the 2nd leading cause of cancer-related mortality in the US, with an estimated 53,000 deaths in 2024. Mutations in the tumor suppressor gene APC, the proto-oncogene KRAS, and the dual tumor suppressor and proto-oncogene TP53 frequently co-occur in human CRC, underscoring its heterogeneity. The DNA damage repair pathway, mediated by the transcription factor p53, promotes cell cycle arrest and apoptosis in response to genotoxic stress. The Ras-MAPK pathway, regulated by the signal transduction protein Ras, triggers cellular proliferation and growth when active. The Wnt pathway, negatively regulated by Adenomatous Polyposis Coli (APC), likewise promotes cellular proliferation and growth through the activity of the transcription factor beta-catenin. The Hippo pathway and JNK pathway have also been found to crosstalk extensively with these pathways, regulating cellular proliferation, cell cycle progression, growth, and cell death. While the individual contributions of these signaling pathways in CRC have been well-documented, additional research is needed to better understand their interactions during tumorigenesis and tumor development. Thus, this study seeks to establish one-hit, two-hit, and three-hit models of CRC in Drosophila and to characterize them for cell cycle defects and altered cell signaling. To generate tumors, MARCM clones were made using escargot-GAL4 to drive the expression of dominant-negative p53, oncogenic RasG12V, and/or loss-of-function APC specifically in intestinal stem cells in early larvae and adult flies. Subsequent phenotypes and gene expression patterns were then assessed via dissection and immunohistochemistry. Here, we present preliminary data from these experiments and our progress in developing preclinical models of CRC in Drosophila.

Publication Date

4-23-2025

Project Designation

Graduate Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship; Practical Wisdom

Drosophila CRC models to study tumor-promoting signaling interactions

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