Abstract C042: Deletion of Gα13 promotes inflammation in the KPC mouse model of pancreatic cancer
Cancer Research(2022)
Abstract
Abstract G protein-coupled receptor (GPCR) signaling regulates many aspects of tumor biology, including inflammation, angiogenesis, and metastasis. However, the tumor-specific functions of G proteins, immediate downstream signaling partners of GPCRs, are not well understood. Counter to previous reports in epithelial cancer cell lines, we recently showed that Gα13, a member of the G12 family of heterotrimeric G proteins, is a tumor suppressor in the genetically engineered KPC (Pdx1-Cre; KrasG12D/+; Tp53R172H/+) mouse model of pancreas cancer (Shields et al., Cell Rep, 2022). Mechanistically, we found that Gα13 loss increases mTOR signaling in mouse and human pancreas tumors and that Gα13-deficient tumors are susceptible to rapamycin. We now show that Gα13 loss in the KPC mouse model is also associated with increased expression of inflammatory cytokines. Moreover, loss of Gα13 also promotes NF-κB signaling and inflammatory cytokines expression in cerulein-driven pancreatitis. Consistently, we find that loss of Gα13 increases the recruitment of macrophages and promotes acinar-ductal metaplasia in cerulein-driven pancreatitis. In our ongoing studies, we are evaluating the role of mTOR signaling in mediating the increased inflammation seen following the loss of Gα13 in our mouse models. Together, our studies show that the tumor-suppressive function of Gα13 is related to the regulation of mTOR signaling and inflammation in pancreas cancer. Citation Format: Mario A. Shields, Anastasia E. Metropulos, Christina Spaulding, Thao ND Pham, Hidayatullah G. Munshi. Deletion of Gα13 promotes inflammation in the KPC mouse model of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C042.
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Key words
pancreatic cancer,gα13,abstract c042,kpc mouse model
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