title: CXCL13-CXCR5 axis promotes the growth and invasion of colon cancer cells via PI3K/AKT pathway.
abstract: CXCL13, an inflammatory factor in the microenvironment, plays a vital role in the progression of inflammatory diseases and tumors. CXCL13 and its receptor CXCR5 have been reported to be associated with poor prognosis of advanced colon cancer. However, the molecular mechanisms of CXCL13-CXCR5 axis in colon cancer remain elusive. The aim of this study was to investigate the role of CXCR5-CXCL13 axis in the growth and invasion of colon cancer cells. Our results showed that CXCL13 promoted the growth, migration, and matrigel invasion of colon cancer cells. Furthermore, CXCL13 increased the expression and secretion of MMP-13, and stimulated the activation of PI3K/AKT pathway. After knockdown of CXCR5 by siRNA, the biological functions of colon cancer cells regulated by CXCL13 were significantly inhibited. In addition, inhibition of PI3K/AKT pathway by specific inhibitor LY294002 suppressed the CXCL13-mediated growth, migration, and invasion of colon cancer cells. Together, our findings suggest that CXCL13-CXCR5 axis promotes the growth, migration, and invasion of colon cancer cells, probably via PI3K/AKT pathway. Thus, CXCL13 may be a useful biomarker for the detection and treatment of colon cancer.
authors.affiliation: Surgiaca Ward 4 (Colorectum & Intestinal Surgery), Shandong Tumor Hospital, Jinan, 250117, Shandong, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xukui
authors.initials: X
authors.lastname: Zhang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Guo
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.forename: Ganlin
authors.initials: G
authors.lastname: Pan
authors.forename: Yinggang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D054382:Chemokine CXCL13 / Q000096:biosynthesis* / Q000235:genetics; D002867:Chromones; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009025:Morpholines; D009361:Neoplasm Invasiveness / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D054380:Receptors, CXCR5 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D054382:Chemokine CXCL13; D002867:Chromones; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D054380:Receptors, CXCR5; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one