title: ERK1/2 signalling pathway is involved in CD147-mediated gastric cancer cell line SGC7901 proliferation and invasion.
abstract: This study aimed to investigate the role of CD147 in the progression of gastric cancer and the signalling pathway involved in CD147-mediated gastric cancer cell line SGC7901 proliferation and invasion. Short hairpin RNA (shRNA) expression vectors targeting CD147 were constructed to silence CD147, and the expression of CD147 was monitored by quantitative realtime reverse transcriptase polymerase chain reaction and Western blot and further confirmed by immunohistochemistry in vivo. Cell proliferation was determined by Cell Counting Kit-8 assay, the activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by gelatin zymography, and the invasion of SGC7901 was determined by invasion assay. The phosphorylation and non-phosphorylation of the mitogen-activated protein kinases, extracellular signal-regulated kinase1/2 (ERK1/2), P38 and c-Jun NH2-terminal kinase were examined by Western blot. Additionally, the ERK1/2 inhibitor U0126 were used to confirm the signalling pathway involved in CD147-mediated SGC7901 progression. The BALB/c nude mice were used to study tumour progression in vivo. The results revealed that CD147 silencing inhibited the proliferation and invasion of SGC7901 cells, and down-regulated the activities of MMP-2 and MMP-9 and the phosphorylation of the ERK1/2 in SGC7901 cells. ERK1/2 inhibitor U0126 decreased the proliferation, and invasion of SGC7901 cells, and down-regulated the MMP-2 and MMP-9 activities. In a nude mouse model of subcutaneous xenografts, the tumour volume was significantly smaller in the SGC7901/shRNA group compared to the SGC7901 and SGC7901/snc-RNA group. Immunohistochemistry analysis showed that CD147 and p-ERK1/2 protein expressions were down-regulated in the SGC7901/shRNA2 group compared to the SGC7901 and SGC7901/snc-RNA group. These results suggest that ERK1/2 pathway involves in CD147-mediated gastric cancer growth and invasion. These findings further highlight the importance of CD147 in cancer progression, indicating that CD147 would be an attractive therapeutic target for gastric cancer.
authors.affiliation: Department of Life Sciences, Nanjing Normal University, Jiangsu Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Pan
authors.forename: Ling
authors.initials: L
authors.lastname: Gu
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Nie
authors.forename: Bangshun
authors.initials: B
authors.lastname: He
authors.forename: Guoqi
authors.initials: G
authors.lastname: Song
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Yeqiong
authors.initials: Y
authors.lastname: Xu
authors.forename: Tianyi
authors.initials: T
authors.lastname: Gao
authors.forename: Shukui
authors.initials: S
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D051926:Basigin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D034741:RNA, Small Interfering; D051926:Basigin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: CD147; extracellular signal-regulated kinase1/2; gastric cancer; invasion; matrix metalloproteinases