Abstract 1766 Mapping nutrient transporter networks in human health and disease

The Wnt signaling pathway governs crucial aspects of cellular processes such as development, differentiation, regeneration, and functioning, including the mesenchymal transition observed in many cancer cell lines.This transition involves the loss of cell polarity and cell-cell adhesion, transforming cells into mesenchymal stem-like states characterized by enhanced motility, drug resistance, tumor growth, and potential for clinical relapse.In the context of colon cancer, particularly in the HCT116 cell line, dysregulated Wnt signaling is frequently observed due to mutations in key pathway genes.This dysregulated pathway plays a critical role in tumorigenesis and progression of colorectal cancer, making HCT116 cells a valuable model for studying Wnt signaling and developing targeted therapies.We aimed to investigate the role of Wnt signaling in these dysregulated pathways utilizing HCT116 cells.In this study, we report that doxorubicin-resistant HCT116 cells exhibit enhancement of many mesenchymal cell characteristics including increased proliferation, motility, anchorage-independent growth, and drug resistance.We further demonstrate that sensitivity to doxorubicin can be restored to resistant cells by targeting Wnt activity with a small molecule (Xav).This study explored the modulation of Wnt activity in HCT116 cells through exposure to toxins and chemotherapy drugs, offering insights into mechanisms of drug resistance and potential strategies for therapeutic intervention.