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

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

doi:10.3389/fphar.2022.777612

Frontiers in Pharmacology (Feb 2022)

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

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

Affiliations

Chao Zhang: Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
Shutao Zhao: Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
Yuen Tan: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
Yuen Tan: Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, Shenyang, China
Siwei Pan: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
Siwei Pan: Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, Shenyang, China
Wen An: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
Wen An: Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, Shenyang, China
Qingchuan Chen: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
Qingchuan Chen: Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, Shenyang, China
Xudong Wang: Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
Huimian Xu: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China
Huimian Xu: Key Laboratory of Gastric Cancer Molecular Pathology of Liaoning Province, Shenyang, China

DOI: https://doi.org/10.3389/fphar.2022.777612
Journal volume & issue: Vol. 13

Abstract

Read online

Background: 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.Methods: 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 in vitro and in vivo.Results: 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. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo 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.Conclusion: 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.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

About the journal

Abstract

Keywords