|Table of Contents|

The mechanisms of erythropoietin-producing hepatocellular A2 protein participating in the invasion of hepatocellular carcinoma cells via regulating the expression of growth factor receptor bound protein 2

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2021 01
Page:
32-37
Research Field:
Publishing date:

Info

Title:
The mechanisms of erythropoietin-producing hepatocellular A2 protein participating in the invasion of hepatocellular carcinoma cells via regulating the expression of growth factor receptor bound protein 2
Author(s):
WANG YananMA QingjiuXU JianqingMAI SaihuHUANG WeihuaYANG XijiaWANG QiFAN WeiweiWANG ShangyuZHOU Liang
Department of General Surgery,Xi'an High-tech Hospital Affiliated to Xi'an Medical College,Shaanxi Xi'an 710075,China.
Keywords:
liver cancererythropoietin-producing hepatocellular A2growth factor receptor bound protein 2invasion
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2021.01.007
Abstract:
Objective:To inquire into the expression and clinical significance of EphA2 protein in the invasion of hepatocellular carcinoma cells, and the possible mechanism of regulating hepatocellular carcinoma cells.Methods:We cultured hepatic cell HL-7702 ,HCC cell lines MHCC97H and Hep3B.The expression of EphA2 and Grb2 in the MHCC97H and Hep3B was suppressed by siRNA interference, and then were divided into three groups:Untreated group,the control group and the siRNA intervention group.The protein expression of EphA2 and Grb2 was explored by Western blot, the invasion ability of MHCC97H and Hep3B was explored by Transwell chamber.Results:The numbers of HL-7702,Hep3B and MHCC97H cells penetrated the watrigel were(31±3)/10 HPF,(111±4)/10 HPF,(401±3)/10 HPF, respectively.There was significant difference in the number between hepatic cell and HCC cell lines(P<0.05).There was significant difference in the protein expression of EphA2 and Grb2 between hepatic cell and HCC cell lines(P<0.05).Suppress the expression of EphA2, the numbers of Hep3B and MHCC97H cells penetrated the Watrigel in the untreated group ,the control group and the siRNA intervention group were(111±4)/10 HPF,(108±5)/10 HPF,(53±3)/10 HPF,and (405±5)/10 HPF,(399±4)/10 HPF,(155±7)/10 HPF.There was significant difference in the number between the control group and the siRNA intervention group(P<0.001).There was significant difference in the protein expression of EphA2 in the MHCC97H and Hep3B cells between the control group and the siRNA intervention group(P<0.05).Suppress the expression of Grb2, the numbers of Hep3B and MHCC97H cells penetrated the watrigel in the untreated group,the control group and the siRNA intervention group were(109±3)/10 HPF,(107±4)/10 HPF,(56±4)/10 HPF and(403±4)/10 HPF,(402±4)/10 HPF,(163±5)/10 HPF.There was significant difference in the number between the control group and the siRNA intervention group(P<0.001).There was significant difference in the protein expression of Grb2 in the MHCC97H and Hep3B cells between the control group and the siRNA intervention group(P<0.05).Suppress the expression of EphA2, there was significant difference in the protein expression of Grb2 in the MHCC97H and Hep3B cells between the control group and the siRNA intervention group(P<0.05).Conclusion:EphA2 may participate in the invasion of HCC cells by regulating the expression of Grb2 protein.EphA2 may be a new target for the treatment of HCC.

References:

[1]王宁,刘硕,杨雷,等.2018全球癌症统计报告解读[J].肿瘤综合治疗电子杂志,2019,5(01):87-97. WANG N,LIU S,YANG L,et al.Interpretation of the 2018 global cancer statistics report[J].Journal of Cancer Comprehensive Therapy,2019,5(01):87-97.
[2]PINTER M,PECK-RADOSAVLJEVIC M.Review article:systemic treatment of hepatocellular carcinoma[J].Alimentary Pharmacology & Therapeutics,2018,48(6):598-609.
[3]LIU Y,YU C,QIU Y,et al.Downregulation of EphA2 expression suppresses the growth and metastasis in squamous-cell carcinoma of the head and neck in vitro and in vivo[J].Journal of Cancer Research and Clinical Oncology,2012,138(2):195-202.
[4]翟道宽,王凤梅,刘辉,等.肝细胞癌组织EphA2表达变化及其促进肿瘤细胞侵袭、转移的机制[J].山东医药,2017,57(24):51-53. ZHAI DK,WANG FM,LIU H,et al.Changes of EphA2 expression in hepatocellular carcinoma and its mechanism of promoting invasion and metastasis of tumor cells[J].Shandong Medicine,2017,57(24):51-53.
[5]张水军,张弓,赵永福,等.EphA2在原发性肝细胞癌中的表达及临床意义[J].中华实验外科杂志,2006,23(03):269-270. ZHANG SJ,ZHANG G,ZHAO YF,et al.Expression and clinical significance of EphA2 in primary hepatocellular carcinoma[J].Chinese Journal of Experimental Surgery,2006,23(03):269-270.
[6]IEGUCHI K,MARU Y.Roles of EphA1/A2 and Ephrin-A1 in cancer[J].Cancer Science,2019,110(3):841-848.
[7]DARLING TK,LAMB TJ.Emerging roles for Eph receptors and Ephrin ligands in immunity[J].Frontiers In Immunology,2019,10:1473.
[8]KOSHIKAWA N,MINEGISHI T,KIYOKAWA H,et al.Specific detection of soluble EphA2 fragments in blood as a new biomarker for pancreatic cancer[J].Cell Death & Disease,2017,8(10):e3134.
[9]RUDNO-RUDZIйSKA J,KIELAN W,FREJLICH E,et al.A review on Eph/Ephrin,angiogenesis and lymphangiogenesis in gastric,colorectal and pancreatic cancers[J].Chinese Journal of Cancer Research,2017,29(4):303-312.
[10]邵伟伟,郝兰香,兰建云,等.EphA2、E-钙黏蛋白在非小细胞肺癌中的表达及意义[J].现代肿瘤医学,2015,23(19):2761-2763. SHAO WW,HAO LX,LAN JY,et al.Expressions and significance of EphA2 and E-cadherin in non-small cell lung cancer[J].Modern Oncology,2015,23(19):2761-2763.
[11]LINDBERG RA,HUNTER T.cDNA cloning and characterization of eck,an epithelial cell receptor protein-tyrosine kinase in the Eph/Elk family of protein kinases[J].Molecular and Cellular Biology,1990,10(12):6316-6324.
[12]MARKOSYAN N,LI J,SUN YH,et al.Tumor cell-intrinsic EPHA2 suppresses antitumor immunity by regulating PTGS2(COX-2)[J].The Journal of Clinical Investigation,2019,129(9):130.
[13]MIYAZAKI T,KATO H,FUKUCHI M,et al.EphA2 overexpression correlates with poor prognosis in esophageal squamous cellcarcinoma[J].International Journal of Cancer,2003,103(5):657-663.
[14]HOU F,YUAN W,HUANG J,et al.Overexpression of EphA2 correlates with epithelial-mesenchymal transition-related proteins in gastric cancer and their prognostic importance for postoperative patients[J].Medical Oncology,2012,29(4):2691-2700.
[15]CUI X,LEE M,KIM J,et al.Activation of mammalian target of rapamycin complex 1(mTORC1) and Raf/Pyk2 bygrowth factor-mediated Eph receptor 2(EphA2) is required for cholangiocarcinoma growth and metastasis[J].Hepatology(Baltimore,Md.),2013,57(6):2248-2260.
[16]KOU CJ,KANDPAL RP.Differential expression patterns of Eph receptors and Ephrin ligands in human cancers[J].BioMed Research International,2018,2018:23.
[17]YANG P,YUAN W,HE J,et al.Overexpression of EphA2,MMP-9,and MVD-CD34 in hepatocellular carcinoma:Implications for tumor progression and prognosis[J].Hepatology Research,2009,39(12):1169-1177.
[18]WU L,ZHANG Y,YE M,et al.Overexpression and correlation of HIF-2α,VEGFA and EphA2 in residual hepatocellular carcinoma following high-intensity focused ultrasound treatment:Implications for tumor recurrence and progression[J].Experimental and Therapeutic Medicine,2017,13(6):3529-3534.
[19]GIUBELLINO A,BURKE TRJ,BOTTARO DP.Grb2 signaling in cell motility and cancer[J].Expert Opinion On Therapeutic Targets,2008,12(8):1021-1033.
[20]YE B,DUAN B,DENG W,et al.EGF stimulates Rab35 activation and gastric cancer cell migration by regulating DENND1A-Grb2 complex formation[J].Frontiers In Pharmacology,2018,9:1343.
[21]ZHU J,LIU Y,HUANG H,et al.MicroRNA-133b/EGFR axis regulates esophageal squamous cell carcinoma metastases by suppressing anoikis resistance and anchorage-independent growth[J].Cancer Cell International,2018,18:193.
[22]WANG X,LU X,ZHANG T,et al.miR-329 restricts tumor growth by targeting Grb2 in pancreatic cancer[J].Oncotarget,2016,7(16):21441-21453.
[23]DING C,TANG W,WU H,et al.The PEAK1-PPP1R12B axis inhibits tumor growth and metastasis by regulating Grb2/PI3K/Akt signalling in colorectal cancer[J].Cancer Lett,2019,442:383-395.

Memo

Memo:
陕西省卫生健康科研基金项目(编号:2018D008)
Last Update: 2020-11-30