Abstract
Abstract Pancreatic ductal adenocarcinoma (PDA) is characterized by intra-tumoral heterogeneity. Using single-cell RNA sequencing, we reveal multiple tumor subpopulations distinguished by their differentiation state and associated with different stages of tumor progression. We identify SPDEF as a factor required for tumorigenesis in pancreatic cancer cells of epithelial and mucinous nature. SPDEF levels correlate with glandular differentiation and high secretory activity, which are characteristic features of human PDA of the classical subtype. SPDEF can drive mucus production in pancreatic cancer cells and is essential for the growth of mucus-secreting tumors by regulating endoplasmic reticulum (ER) activity. These findings offer insights into the factors controlling differentiation in PDA and may inform new therapeutic strategies with improved efficacy. Citation Format: Claudia Tonelli, Georgi N. Yordanov, Yuan Hao, Astrid Deschênes, Erin Brosnan, Abishek Doshi, Youngkyu Park, Jonathan Preall, David A. Tuveson. The transcription factor SPDEF promotes the survival of mucinous pancreatic ductal adenocarcinoma of the classical subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6081.
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