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野生型 KRAS 通过 Wnt/β-连环蛋白途径抑制胰腺癌的迁移和侵袭。

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

机构信息

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.

出版信息

Mol Med Rep. 2023 Jan;27(1). doi: 10.3892/mmr.2022.12891. Epub 2022 Nov 11.

DOI:10.3892/mmr.2022.12891
PMID:36367161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9673065/
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) has a survival advantage in PDAC and can antagonize the effect of mutated KRAS G12D (KRAS), leading to a low cell transformation efficiency. The present study focused on the differences in biological behavior between KRAS and KRAS and explored the mechanism in pancreatic cancer. Overexpressed KRAS and KRAS 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. , the proliferation of KRAS group was reduced compared with PANC‑1 group, while the proliferation of KRAS group was not significantly changed. , the proliferation of KRAS group was reduced and that of KRAS group was enhanced compared with that in the PANC‑1 group. The invasion and migration of KRAS group were decreased, while the invasion and migration of KRAS 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 group was increased, while no significant difference was observed in KRAS group. The results of immunohistochemistry were consistent with those of western blotting. KRAS group can inhibit the proliferation of pancreatic cancer and , while KRAS group can significantly promote proliferation , but not significantly in vitro. Wild‑type KRAS may inhibit the invasion and migration of pancreatic cancer through the Wnt/β‑catenin pathway.

摘要

Kirsten 大鼠肉瘤病毒 (KRAS) 突变被认为是导致胰腺导管腺癌 (PDAC) 发生的事件，KRAS 基因突变在 PDAC 中的突变频率为 90-95%。研究表明，野生型 KRAS (KRAS) 在 PDAC 中具有生存优势，并且可以拮抗突变型 KRAS G12D (KRAS) 的作用，导致细胞转化效率低。本研究重点关注 KRAS 和 KRAS 之间的生物学行为差异，并探讨了在胰腺癌中的机制。通过慢病毒转染将过表达的 KRAS 和 KRAS 转染到细胞中。通过细胞计数试剂盒-8 (CCK-8)、克隆形成、划痕愈合和 Transwell 分析以及裸鼠肿瘤形成实验，探讨了差异和机制。结果表明，与 PANC-1 组相比，KRAS 组的增殖减少，而 KRAS 组的增殖没有明显变化。与 PANC-1 组相比，KRAS 组的增殖减少，KRAS 组的增殖增强。KRAS 组的侵袭和迁移减少，而 KRAS 组的侵袭和迁移增加。Western blot 显示，KRAS 组中 E-钙黏蛋白、α-E-连环蛋白、MMP-3、MMP-9、STAT3 和磷酸化 STAT3 的表达增加，而 KRAS 组无明显差异。免疫组化结果与 Western blot 一致。KRAS 组可抑制胰腺癌的增殖和转移，而 KRAS 组可显著促进增殖，但体外不明显。野生型 KRAS 可能通过 Wnt/β-连环蛋白通路抑制胰腺癌的侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/e025f626e560/mmr-27-01-12891-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/b8b17238aa35/mmr-27-01-12891-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/07576dabe085/mmr-27-01-12891-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/382af41388bc/mmr-27-01-12891-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/2d6cd7b5fd14/mmr-27-01-12891-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/ac0f0da969de/mmr-27-01-12891-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/fb42ea398a53/mmr-27-01-12891-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/631e13468f41/mmr-27-01-12891-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/e025f626e560/mmr-27-01-12891-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/b8b17238aa35/mmr-27-01-12891-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/07576dabe085/mmr-27-01-12891-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/382af41388bc/mmr-27-01-12891-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/2d6cd7b5fd14/mmr-27-01-12891-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/ac0f0da969de/mmr-27-01-12891-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/fb42ea398a53/mmr-27-01-12891-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/631e13468f41/mmr-27-01-12891-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22b/9673065/e025f626e560/mmr-27-01-12891-g07.jpg

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