MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway

Journal of Gastrointestinal Oncology

article

Yajun Qi¹  Qilu Fang¹  Qinglin Li³  Haiying Ding¹  Qi Shu¹  Yan Hu¹  Wenxiu Xin¹  Luo Fang¹ 

[1] Department of Pharmacy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital);Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences;Department of Comprehensive Medical Oncology, Key Laboratory of Head and Neck Translational Research of Zhejiang Province, Zhejiang Cancer Hospital

关键词: Hepatocellular carcinoma (HCC);    myeloid differentiation protein 2 (MD2);    epidermal growth factor receptor (EGFR);    migration;    invasion;   

DOI  :  10.21037/jgo-21-362

学科分类：肿瘤学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: The toll-like receptor (TLR) is an emerging signaling pathway in tumor invasion and metastasis. The activation of TLRs requires specific accessory proteins, such as the small secreted glycoprotein myeloid differentiation protein 2 (MD2), which contributes to ligand responsiveness. However, the role of MD2 in tumorigenesis and metastasis has rarely been reported. This study aimed to investigate the effects and underlying mechanisms of MD2 on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC).Methods: Cell counting kit 8 (CCK8), cell colony formation, wound healing, and transwell assays were conducted to determine cell viability, proliferation, migration, and invasion, respectively. Quantitative real-time PCR (qRT-PCR) was performed to assess the expression of MD2 in HCC cell lines and human normal liver cell lines as well as the silencing efficiency of MD2 blockage. Western blot and qRT-PCR assays were performed to detect the protein and mRNA expression levels of epithelial mesenchymal transformation (EMT) markers and epidermal growth factor receptor (EGFR) signaling molecules.Results: MD2 was highly expressed in HCC tissues and cell lines. High expression of MD2 was associated with poor prognosis of HCC patients. In addition, MD2 silencing slightly inhibited the proliferation of HepG2 and HCCLM3, and significantly suppressed cell migration and invasion. Furthermore, MD2 blockage could distinctly prevent the EMT process by increasing the protein and mRNA levels of E-cadherin and Occludin, and decreasing the levels of Vimentin, N-cadherin, and Snail. Finally, the phosphorylation level of EGFR as well as its downstream molecular Src, Akt, I-κBα, and p65 were downregulated in HCC cells with MD2 silencing.Conclusions: Our findings suggest that high expression of MD2 may affect the EMT, migration, and invasion via modulation of the EGFR pathway in HCC cells.

【 授权许可】

Unknown