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

doi:10.21037/jgo-21-362

	MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway
	Qi, Yajun 1,3; Fang, Qilu 1,3; Li, Qinglin 1,2; Ding, Haiying 3; Shu, Qi 1,3; Hu, Yan 1,3; Xin, Wenxiu 1,2,3; Fang, Luo 1,3
刊名	JOURNAL OF GASTROINTESTINAL ONCOLOGY
	2021-07-29
关键词	Hepatocellular carcinoma (HCC) myeloid differentiation protein 2 (MD2) epidermal growth factor receptor (EGFR) migration invasion
ISSN号	2078-6891
DOI	10.21037/jgo-21-362
通讯作者	Xin, Wenxiu(xinwx@zjcc.org.cn) ; Fang, Luo(fangluo@zjcc.org.cn)
英文摘要	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 realtime 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-Kappa B alpha, 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.
资助项目	National Natural Science Foundation of China[81903898] ; National Natural Science Foundation of China[81773819] ; National Natural Science Foundation of China[81973396] ; National Natural Science Foundation of China[82003851] ; Zhejiang Provincial Natural Science Foundation of China[YY19H310003] ; Medical Science and Technology Program of Zhejiang province[2013KYA027] ; Medical Science and Technology Program of Zhejiang province[2017190933] ; Medical Science and Technology Program of Zhejiang province[2016KYB038] ; Medical Science and Technology Program of Zhejiang province[2019ZD024] ; Medical Science and Technology Program of Zhejiang province[2019KY037]
WOS关键词	TOLL-LIKE RECEPTORS ; TARGETING EMT ; CANCER CELLS ; COLON-CANCER ; E-CADHERIN ; TLR4 ; LIPOPOLYSACCHARIDE ; EXPRESSION ; ANTAGONIST ; SURVIVAL
WOS研究方向	Oncology ; Gastroenterology & Hepatology
语种	英语
出版者	AME PUBL CO
WOS记录号	WOS:000684453400001
资助机构	National Natural Science Foundation of China ; Zhejiang Provincial Natural Science Foundation of China ; Medical Science and Technology Program of Zhejiang province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/124290]
专题	中国科学院合肥物质科学研究院
通讯作者	Xin, Wenxiu; Fang, Luo
作者单位	1.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou, Peoples R China 2.Zhejiang Canc Hosp, Dept Comprehens Med Oncol, Key Lab Head & Neck Translat Res Zhejiang Prov, Hangzhou, Peoples R China 3.Univ Chinese Acad Sci, Dept Pharm, Canc Hosp, Zhejiang Canc Hosp, 1 Banshan Rd, Hangzhou 310022, Peoples R China
推荐引用方式 GB/T 7714	Qi, Yajun,Fang, Qilu,Li, Qinglin,et al. MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway[J]. JOURNAL OF GASTROINTESTINAL ONCOLOGY,2021.
APA	Qi, Yajun.,Fang, Qilu.,Li, Qinglin.,Ding, Haiying.,Shu, Qi.,...&Fang, Luo.(2021).MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway.JOURNAL OF GASTROINTESTINAL ONCOLOGY.
MLA	Qi, Yajun,et al."MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway".JOURNAL OF GASTROINTESTINAL ONCOLOGY (2021).