Colorectal cancer (CRC) is characterized by a high mutational burden and complex genetic interactions that contribute to tumorigenesis, therapeutic resistance, and immune evasion. This study combines literature analysis with bioinformatic database query (via cBioPortal and Metascapes) to investigate how the overproduction of β-catenin contributes to CRC progression and therapeutic resistance, with the goal of identifying novel combinatorial treatment strategies. In the Wnt β-catenin signaling pathway, both APC mutations and the loss of E-cadherin drive aberrant production of β-catenin, promoting uncontrolled cell proliferation and chemoresistance. Normally, the β-catenin directly binds to the intracellular domain of E-cadherin, forming a complex essential for cell-cell adhesion and epithelial tissue integrity. In CRC, the β-catenin-E-cadherin link shifts from maintaining cell-cell adhesion to driving tumor progression, as the buildup of β-catenin in the cytoplasm results in less β-catenin at E-cadherin junctions. Combined with the overall loss of E-cadherin and β-catenin accumulation in the cytoplasm, this dysregulated process allows nuclear translocation to activate pro-invasive genes, driving CRC development. Finally, this study investigates the effects and potential treatments targeting APC mutations and the β-catenin-E-cadherin link and its effect on the proliferation of CRC by proposing a potential therapeutic strategy. By detailing a synthetic biology approach to reintroduce functional APC protein in colorectal cancer (CRC) models to restore regulation of β-catenin and reinforce E-cadherin–mediated cell adhesion. By reactivating normal Wnt signaling dynamics, this strategy aims to suppress uncontrolled proliferation and strengthen epithelial integrity compromised by APC loss.
Hadassah Ho (Fri,) studied this question.