BUD31 and Lipid Metabolism: A New Potential Therapeutic Entry Point for Myc-Driven Breast Cancer
Abstract
Myc activation is common in breast cancer, correlated with triple negative disease, and associated with mortality. Thus, understanding Myc-driven breast cancer will facilitate knowledge of triple negative disease, a subtype of breast cancer with poor outcome and limited treatment options. Myc confers both pro- and anti-tumorigenic effects on cells suggesting a sensitive balancing act for survival downstream of Myc activation. Supporting pathways, while not oncogenic by themselves, are necessary to help cells tolerate Myc driven stresses. Since direct pharmacological targeting of Myc has been shown to be largely unsuccessful, our laboratory has performed a genome-wide RNAi screen to identify supporting genes that are required to tolerate Myc activation in human mammary epithelial cells (Kessler et al.). Through this screen, we have identified BUD31, a poorly understood gene, and components of the fatty acid oxidation pathway (hereafter FAMs- fatty acid oxidation Myc synthetic lethal genes) as required for tolerance of Myc driven stress and as putative new therapeutic entry points for Myc-driven breast cancer. Our preliminary data indicate that BUD31 physically interacts with FAMs suggesting a functional relationship between the two. Objective/Hypothesis: Based on these preliminary data, we hypothesize that Myc activation confers a dependence on BUD31 and FAMs for breast cancer survival through a mechanism involving physical and functional interaction between BUD31 and fatty acid oxidation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2015
- Accession Number
- ADA619281
Entities
People
- Sarah Kurley
Organizations
- Baylor College of Medicine