Wild‑type KRAS inhibits the migration and invasion of pancreatic cancer through the Wnt/β‑catenin pathway

Hu,Xianhua; Zhang,Rendan; Yao,Jiaxin; Mu,Bo; Zhao,Chunyan

doi:10.3892/mmr.2022.12891

Wild‑type KRAS inhibits the migration and invasion of pancreatic cancer through the Wnt/β‑catenin pathway

Authors:
- Xianhua Hu
- Rendan Zhang
- Jiaxin Yao
- Bo Mu
- Chunyan Zhao
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Affiliations: Department of Medical Laboratory, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, School of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Sichuan Key Laboratory of Medical Imaging, Institute of Medical Imaging, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: November 7, 2022 https://doi.org/10.3892/mmr.2022.12891
Article Number: 4
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Kirsten rat sarcoma virus (KRAS) mutation is considered to be the event that leads to the initiation of pancreatic ductal adenocarcinoma (PDAC), the mutation frequency of the KRAS gene in PDAC is 90‑95%. Studies have shown that wild‑type KRAS (KRAS^WT) has a survival advantage in PDAC and can antagonize the effect of mutated KRAS G12D (KRAS^G12D), leading to a low cell transformation efficiency. The present study focused on the differences in biological behavior between KRAS^WT and KRAS^G12D and explored the mechanism in pancreatic cancer. Overexpressed KRAS^WT and KRAS^G12D was transfected into cells through lentiviral transfection. The differences and mechanisms were explored using cell counting kit‑8 (CCK‑8), clone formation, wound healing and Transwell assays, as well as western blotting, immunohistochemistry and tumor formation in nude mice. In vitro, the proliferation of KRAS^WT group was reduced compared with PANC‑1 group, while the proliferation of KRAS^G12D group was not significantly changed. In vivo, the proliferation of KRAS^WT group was reduced and that of KRAS^G12D group was enhanced compared with that in the PANC‑1 group. The invasion and migration of KRAS^WT group were decreased, while the invasion and migration of KRAS^G12D group were increased. Western blotting showed that the expression of E‑cadherin, α‑E‑catenin, MMP‑3, MMP‑9, STAT3 and phosphorylated STAT3 in KRAS^WT group was increased, while no significant difference was observed in KRAS^G12D group. The results of immunohistochemistry were consistent with those of western blotting. KRAS^WT group can inhibit the proliferation of pancreatic cancer in vitro and in vivo, while KRAS^G12D group can significantly promote proliferation in vivo, but not significantly in vitro. Wild‑type KRAS may inhibit the invasion and migration of pancreatic cancer through the Wnt/β‑catenin pathway.

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