SHP-2 Interacts with CD8I and Regulates the Malignant Evolution of Colorectal Cancer by Inhibiting Epithelial--Mesenchymal Transition

• Published in: Cancer management and research Vol. 12; p. 13273
• Main Authors: Yuan, Huaqin, Zhao, Jun, Yang, Yang, Wei, Rongfu, Zhu, Liangxue, Wang, Jie, Ding, Meiqing, Wang, Mingyun, Gu, Yanhong
• Format: Journal Article
• Language: English
• Published: Dove Medical Press Limited 31-12-2020
• Subjects: Apoptosis; Colorectal cancer; Metastasis; Phosphatases; Stem cells; Tyrosine; China
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S270813

Purpose: 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 Realtime 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