Investigating the role of the Wnt/ß-catenin pathway effector Tcf7l2, in colon adenoma organoids

• Main Author: Lee, Xin Er
• Other Authors: Ruedl Christiane
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2020
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/141793
• Institution: Nanyang Technological University

Tcf7l2 has been an interest of colon research due to its key role in Wnt/ß-catenin pathway and in colorectal cancer. With colon cancer being highly fatal in developed countries, it is crucial to find alternative treatments for colon cancer that are less toxic, more targeted and effective. Tcf7l2 is a major Wnt effector that effectuates Wnt signalling responsible for intestinal homeostasis. Despite controversies for the significance of Tcf7l2’s contribution to colon cancer development, it is undeniable that Tcf7l2 promotes cell proliferation under Wnt activation. In this report, effects of Tcf7l2 suppression were studied on colon organoids – healthy and adenomatous. Multiple factors contribute to sporadic and familial colorectal cancer. With APCMin allele accounting for most cases, colon adenoma can be studied through use of APCMin/- organoids. The organoids in this experiment were designed for Tcf7l2 to be regulated under the Tet-inducible expression system. High Tcf7l2 suppression was revealed to reduce proliferation and increase secretory cells in healthy colon organoids. In colon adenoma organoids, Tcf7l2, though physiologically expressed at lower levels, responds to Tcf7l2 suppression, displaying lowered proliferation and recovered some morphology to that of healthy colon organoids. Hence, Tcf7l2 presents as a potential therapeutic target for earlystage colon cancer treatment.