SHP-2 Interacts with CD81 and Regulates the Malignant Evolution of Colorectal Cancer by Inhibiting Epithelial–Mesenchymal Transition

Abstract

Huaqin Yuan,1,* Jun Zhao,2,* Yang Yang,3 Rongfu Wei,1 Liangxue Zhu,1 Jie Wang,1 Meiqing Ding,1 Mingyun Wang,1 Yanhong Gu4 1Department of Oncology, Nanjing Gaochun People’s Hospital Affiliated to Yangzhou University, Nanjing, Jiangsu 211316, People’s Republic of China; 2Department of Orthopedics, Nanjing Gaochun People’s Hospital Affiliated to Yangzhou University, Nanjing, Jiangsu 211316, People’s Republic of China; 3Department of Oncology, Gulou Hospital Affiliated to Medical College of Nanjing University, Nanjing, Jiangsu 210000, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, People’s Republic of China*These authors contributed equally to this work.Correspondence: Mingyun WangDepartment of Oncology, Nanjing Gaochun People’s Hospital Affiliated to Yangzhou University, 53 Maoshan Road, Gaochun, Nanjing, Jiangsu 211316, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] GuDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Colon cancer is a common malignant tumor of the digestive system. This project verified the negative role of protein tyrosine phosphatase (SHP-2) in the regulation of colon cancer and further clarified the key targets and molecular mechanisms in the regulation process.Patients and Methods: The expression levels of SHP-2 in colon cancer tissues, adjacent tissues, normal colon cell lines, and cancer cell lines were detected via Quantitative Real-time PCR (qRT-PCR). The effect of SHP-2 on colon cancer cell function was verified using cell proliferation, Transwell, scratch, and apoptotic assays. CD81 was identified as the interaction protein of SHP-2 by immunoprecipitation.Results: The expression of SHP-2 was decreased in colorectal cancer compared with that in adjacent tissues. This expression was also decreased in colon cancer cells compared with that in intestinal epithelial cells. In addition, the tumor tissues of patients with metastatic colon cancer exhibited downregulated expression of SHP-2 compared with those of patients with non-metastatic colon cancer. Cell proliferation, Transwell, scratch, and apoptotic assay showed that the overexpression of SHP-2 inhibited proliferation, adhesion, and metastasis of colon cancer cell lines and promoted apoptosis. CO-IP proved that SHP-2 could interact with CD81 and inhibit the function of CD81. Recovery experiments confirmed that the overexpression of CD81 reversed the anti-cancer effect of SHP-2.Conclusion: Overexpression of SHP-2 inhibited malignant progression of colon cancer. Mechanism experiments showed that the anti-cancer effect of SHP-2 was realized through the interaction with CD81. This study elucidated the molecular mechanism of SHP-2 regulation in colon cancer and provided guidance for the diagnosis and prognosis assessment of colon cancer.Keywords: SHP-2, CD81, EMT, colorectal cancer

Keywords

• shp-2
• cd81
• emt
• colorectal cancer