title: CXCL10/CXCR3 axis promotes the invasion of gastric cancer via PI3K/AKT pathway-dependent MMPs production.
abstract: CXCR3, a G-protein coupled chemokine receptor, has been found to be overexpressed in many tumors and act as an independent prognostic marker. However, it is still unclear whether CXCR3 is involved in gastric cancer progression. In this study, we found that CXCR3 was markedly expressed in gastric cancer cells and tissues. High CXCR3 expression correlated with advanced tumor stage, vascular invasion, lymph node metastasis and poor survival of gastric cancer patients. Activation of CXCR3 by one of its ligands CXCL10 promoted the invasion and migration of gastric cancer BGC-823 and MGC-803 cells, and increased the secretion and activities of MMP-2 and MMP-9. However, the effects of CXCL10 on gastric cancer cells were attenuated by CXCR3 siRNA transfection. Furthermore, overexpression of CXCR3 enhanced CXCL10-mediated cell invasion and migration of gastric cancer MKN28 cells. In addition, CXCR3 time-dependently induced activation of AKT. PI3K/AKT pathway was required for CXCR3-mediated gastric cancer cell invasion, migration and MMP-2/9 production. Together, our findings suggest that CXCL10/CXCR3 axis promotes gastric cancer cell invasion and migration by upregulating MMP-2 and MMP-9 production via PI3K/AKT pathway. Thus, CXCR3 could be a potential target for the gastric cancer treatment.
authors.affiliation: Department of 7th Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of 7th Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of 7th Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of 7th Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of 7th Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang Province, China. Electronic address: danliunn@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D054357:Chemokine CXCL10 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: CXCL10; CXCR3; Invasion; MMPs; Migration; PI3K/AKT