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SKA3-DUSP2轴通过激活MAPK/ERK途径促进胃癌肿瘤发生和上皮-间质转化。

The SKA3-DUSP2 Axis Promotes Gastric Cancer Tumorigenesis and Epithelial-Mesenchymal Transition by Activating the MAPK/ERK Pathway.

作者信息

Zhang Chao, Zhao Shutao, Tan Yuen, Pan Siwei, An Wen, Chen Qingchuan, Wang Xudong, Xu Huimian

机构信息

Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China.

Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

Front Pharmacol. 2022 Feb 28;13:777612. doi: 10.3389/fphar.2022.777612. eCollection 2022.

Abstract

Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied. The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied and . Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer. Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.

摘要

纺锤体和动粒相关复合体亚基3(SKA3)是SKA蛋白家族的成员之一,与多种癌症的进展相关。然而,SKA3在胃癌中的作用尚未得到研究。通过免疫组织化学检测SKA3和双特异性磷酸酶2(DUSP2)蛋白的表达水平。研究了SKA3和DUSP2对胃癌增殖、迁移、侵袭、黏附及上皮-间质转化的影响。对164例胃癌进行免疫组织化学分析发现,SKA3高表达与DUSP2表达呈负相关,且与N分期、腹膜转移及预后不良相关。研究表明,沉默SKA3表达可抑制胃癌的增殖、迁移、侵袭、黏附及上皮-间质转化。实验表明,沉默SKA3可抑制肿瘤生长和腹膜转移。机制上,SKA3负向调节肿瘤抑制因子DUSP2并激活MAPK/ERK通路以促进胃癌发生。我们的数据表明,SKA3-DUSP2-ERK1/2轴参与胃癌进展的调控,且SKA3是胃癌潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/308e/8918524/7b15ae885833/fphar-13-777612-g001.jpg

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