Abstract 171: ERK dynamics are essential for colon tissue patterning

Abstract

Abstract Maintaining the correct ratio of cellular niches in space and time allows tissues to perform their complex functions and create patterns. This maintenance of tissue patterning is often dysregulated during cancer development. In order to study tissue patterning, temporal and spatial resolution of communication between single cells is required. To explore how this complex process is controlled, we developed a patient-derived organoid screening platform to study both tissue patterning and kinase pathway dynamics in single cells across hundreds of conditions. Unlike normal and polyp-derived organoids, tumor organoids displayed a lack of patterning reminiscent of in vivo dysplasia. Using this system, we discovered that waves of Erk signaling induced by apoptotic cells are critical for maintaining tissue patterning in human colonic organoids. Using a small molecule-based screen, we discovered novel kinases which limit Erk activation across tissues and help maintain patterning. Perturbation of Erk restricting kinases results in dysfunctional colonic wound repair and re-establishment of tissue patterns in vivo. Citation Format: Kelvin W. Pond, Jayati Chakrabarti, Curtis A. Thorne, Andrew L. Paek. ERK dynamics are essential for colon tissue patterning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 171.