title: The cell surface GRP78 facilitates the invasion of hepatocellular carcinoma cells.
abstract: Invasion is a major characteristic of hepatocellular carcinoma and one of the main causes of refractory to treatment. We have previously reported that GRP78 promotes the invasion of hepatocellular carcinoma although the mechanism underlying this change remains uncertain. In this paper, we explored the role of the cell surface GRP78 in the regulation of cancer cell invasion in hepatocellular carcinoma cells. We found that neutralization of the endogenous cell surface GRP78 with the anti-GRP78 antibody inhibited the adhesion and invasion in hepatocellular carcinoma cell lines Mahlavu and SMMC7721. However, forced expression of the cell surface GRP78 facilitated the adhesion and invasion in SMMC7721. We further demonstrated that inhibition of the endogenous cell surface GRP78 specifically inhibited the secretion and activity of MMP-2 but did not affect the secretion and activity of MMP-9. We also found that inhibition of the cell surface GRP78 increased E-Cadherin expression and decreased N-Cadherin level. On the contrary, forced expression of the cell surface GRP78 increased N-Cadherin expression and decreased E-Cadherin level, suggesting that the cell surface GRP78 plays critical role in the regulation of EMT process. These findings suggest that the cell surface GRP78 plays a stimulatory role in the invasion process and may be a potential anti-invasion target for the treatment of hepatocellular carcinoma.
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China ; Oncology Department, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Xiu-Xiu
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Hong-Dan
authors.initials: HD
authors.lastname: Li
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Song
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Traditional Chinese Department, The First Affiliated Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Guo
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China ; Developmental Biology Department, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Luan
authors.affiliation: Central Laboratory, Liaoning Medical College, Jinzhou, Liaoning 121001, China ; Medical Genetics Department, Liaoning Medical College, Jinzhou, Liaoning 121001, China.
authors.forename: Rong-Jian
authors.initials: RJ
authors.lastname: Su
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000502:physiology
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9