The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice
Megan T. Hoffman, Samantha B. Kemp, Daniel James Salas-Escabillas, Yaqing Zhang, Nina G. Steele, Stephanie The, Daniel D. Long, Simone Benitz, Yan Wei, Robert F. Margolskee, Filip Bednar, Marina Pasca di Magliano, Hui‐Ju Wen, Howard C. Crawford
Abstract
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA) initiation and progression are accompanied by an immunosuppressive inflammatory response. Here, we evaluated the immunomodulatory role of chemosensory signaling in metaplastic tuft cells (MTCs) by analyzing the role of GNAT3, a gustatory pathway G-protein expressed by MTCs, during PDA progression. METHODS: ;KC mice were aged to morbidity or 52 weeks. RESULTS: ;KC mice progressed more rapidly to metastatic carcinoma compared with KC controls. CONCLUSIONS: Compromised gustatory sensing, achieved by Gnat3 ablation, enhanced the CXCL1/2-CXCR2 axis to alter the MDSC population and promoted the progression of metastatic PDA.