Objectives/Goals: To determine the role of carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in signaling cascade and interaction with other cell surface proteins in human epithelial solid tumors such pancreatic adenocarcinoma and colon cancer Methods/Study Population: In this study, we employed three-dimensional (3D) tumor models to replicate the in vivo tumor microenvironment better, allowing for a more accurate assessment of cellular responses compared to traditional two-dimensional (2D) cultures. We used immunoprecipitate to pull down the CEACAM6 protein and investigate the integrins expression level. Results/Anticipated Results: The expression and functional activity of CEACAM6 are susceptible to modulation by various surface proteins, leading to notable alterations in cellular behavior. Integrins, particularly Integrin B4, are one such protein whose expression is influenced by CEACAM6-mediated intracellular signaling cascades, suggesting a complex interplay that enhances CEACAM6 activation.The 3D models facilitate cell–cell interactions, enabling tumor cells to proliferate and undergo metabolic changes that reflect actual tumor biology. Thereby enhancing the relevance of crosstalk between CEACAM6 and integrins. These findings underscore the potential of CEACAM6 as a promising therapeutic target. They reveal a molecular mechanism that could inform the development of innovative therapeutic strategies in cancer. Discussion/Significance of Impact: These findings underscore the potential of CEACAM6 as a promising therapeutic target, revealing a novel molecular mechanism that could inform the development of innovative therapeutic strategies for pancreatic and colon cancer and potentially other malignancies.