Abstract 493: Cingulin plays a role in PDAC organoid polarity and subtype

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a dismal five-year survival rate of 12.5%. Our lab previously identified two transcriptomic PDAC tumor subtypes, termed basal-like and classical. Basal-like tumors are more aggressive while classical tumors have a better prognosis and are more sensitive to chemotherapy. However, many of the biological differences and drivers of the two subtypes remain unknown. We defined the proteomic landscape of PDAC tumors and found that classical tumors are enriched for cell polarity processes compared to basal-like tumors, and that one of the significantly enriched polarity proteins in classical PDAC tumors was cingulin (CGN). Classical organoids recapitulate the well-differentiated architecture of classical PDAC with well-organized hollow lumens. We found that CGN is required for the well-differentiated architecture of classical PDAC organoids and overexpression of CGN is sufficient to drive basal-like organoids to a more well-differentiated state. Additionally, overexpression of CGN in basal-like cell lines decreased invasion. Our results indicate CGN plays a role in PDAC organoid polarity, subtype, and aggression and further study could increase our understanding of the biological differences between PDAC subtypes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 493.