High Expression of ITGA3 Promotes Proliferation and Cell Cycle Progression and Indicates Poor Prognosis in Intrahepatic Cholangiocarcinoma

Author:

Huang Yu12,Kong Yang12,Zhang Lufei12ORCID,He Tianyu12,Zhou Xiaohu12,Yan Yingcai12,Zhang Linshi12,Zhou Dongkai12,Lu Sinan12,Zhou Jiarong12,Zhou Lin3,Xie Haiyang3,Zheng Shusen234ORCID,Wang Weilin124ORCID

Affiliation:

1. Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

2. Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

3. Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

4. State Key Laboratory & Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Abstract

Integrin subunit alpha 3 (ITGA3) interacts with a beta 1 subunit to form a member of the integrin family. Integrins are heterodimeric integral membrane proteins that serve as cell surface adhesion proteins. In this research, we investigated the biological function of this protein in human intrahepatic cholangiocarcinoma (ICC) for the first time. Here, using Western blotting and immunohistochemistry assays, we discovered that ITGA3 was overexpressed in ICC cell lines and ICC patients. Moreover, we found ITGA3 expression correlated with several clinicopathological features, including tumor size, lymph node metastasis, and the TNM stage. Patients with high ITGA3 expression underwent a worse prognosis after complete resection compared with patients with low ITGA3 expression in terms of overall survival. Furthermore, we demonstrated that ITGA3 could significantly promote ICC cell proliferation and cell cycle progression in vitro. However, as a classical cell surface adhesion molecule, we found ITGA3 correlated negatively with the migration and invasion of ICC cell lines, which differs from other malignant tumors. Generally, these findings suggest that ITGA3 may play a role as a potential oncogene in ICC and suppression of ITGA3 expression may establish a novel target for guiding the therapy of ICC patients.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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