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敲低Kremen2可抑制胃癌的肿瘤生长和迁移。

Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer.

作者信息

Chen Beibei, Wang Sai-Qi, Huang Jinxi, Xu Weifeng, Lv Huifang, Nie Caiyun, Wang Jianzheng, Zhao Huichen, Liu Yingjun, Li Jitian, Lu Canrong, Zhang Jianying, Chen Xiao-Bing

机构信息

Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.

出版信息

Front Oncol. 2021 Jan 7;10:534095. doi: 10.3389/fonc.2020.534095. eCollection 2020.

DOI:10.3389/fonc.2020.534095
PMID:33489867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7817645/
Abstract

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival and tumorigenesis of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G/M phase and repression of migration in gastric cancer cells . Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

摘要

Kremen2（Krm2）作为经典Wnt/β-连环蛋白信号通路的关键调节因子，在胚胎发育、骨形成和肿瘤发生中发挥着重要作用。然而，Krm2在胃癌中的作用尚不清楚。本研究旨在探讨Krm2在胃癌发生和转移中的调节作用。结果表明，与癌旁组织相比，Krm2在胃癌组织中显著上调，且与胃癌患者的病理分级呈正相关。鉴于Krm2在大多数检测的胃癌细胞系中大量表达，我们建立了Krm2敲低细胞模型，并进一步用于构建小鼠异种移植模型。敲低Krm2后，胃癌细胞的存活率和肿瘤发生均受到抑制。同时，敲低Krm2诱导胃癌细胞凋亡、细胞周期阻滞于G/M期并抑制细胞迁移。机制上，我们发现敲低Krm2可抑制PI3K/Akt通路。因此，我们揭示了Krm2在促进胃癌发生和转移中的新作用及分子机制。Krm2可能是设计靶向治疗的有力候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/ec9cda38aa1b/fonc-10-534095-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/79f02d2d2c33/fonc-10-534095-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/202f5c6ffbbd/fonc-10-534095-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/8ef0e8fa3240/fonc-10-534095-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/ec1e1613f335/fonc-10-534095-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/5407a06173ee/fonc-10-534095-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/ec9cda38aa1b/fonc-10-534095-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/79f02d2d2c33/fonc-10-534095-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/202f5c6ffbbd/fonc-10-534095-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/8ef0e8fa3240/fonc-10-534095-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/ec1e1613f335/fonc-10-534095-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/5407a06173ee/fonc-10-534095-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0724/7817645/ec9cda38aa1b/fonc-10-534095-g006.jpg

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