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bioRxiv · 10.1101/2021.03.15.435488

Gα13 loss promotes tumor progression in the KPC transgenic mouse model of advanced pancreatic cancer

Shields, M. A.·Spaulding, C.·Khalafalla, M. G.·Pham, T. N.·Munshi, H. G.
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Abstract

G13 transduces signals from G protein-coupled receptors. G13 is pro-tumorigenic in epithelial cancer cell lines, which contrasts with its tumor-suppressive function in transgenic mouse models of lymphomas. Here we show that while loss of G13 in pancreatic cell lines decreases tumor growth in vivo, G13 loss in the Kras-driven (KC) mouse model of pancreatic tumor initiation does not affect tumor development or survival. Instead, G13 loss in the Kras/Tp53 (KPC) transgenic mouse model of advanced pancreatic cancer promotes well-differentiated tumors with increased tumor burden and reduced survival. Mechanistically, G13 loss in the KPC mouse model enhances E-cadherin-mediated cell-cell junctions and mTOR signaling. Importantly, human pancreatic cancers with low G13 expression exhibit increased E-cadherin protein expression and mTOR signaling. This work establishes a context-dependent role of G13 in pancreatic tumorigenesis, demonstrating a tumor-suppressive role in transgenic mouse models of advanced pancreatic cancer.

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Shields, M. A., Spaulding, C., Khalafalla, M. G., Pham, T. N., Munshi, H. G.. 2021-03-15. Gα13 loss promotes tumor progression in the KPC transgenic mouse model of advanced pancreatic cancer. https://doi.org/10.1101/2021.03.15.435488

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