title: Sphingosine kinase 1 promotes tumor progression and confers malignancy             phenotypes of colon cancer by regulating the focal adhesion kinase pathway and             adhesion molecules.
abstract: Studies suggest a tumor-promoting function of sphingosine kinase 1 (SphK1)             in some types of human tumors, however, its effect on colon cancer is still unclear.             The aims of this study were to investigate the roles of SphK1 in the progression             and tumor cell phenotypic changes in colon cancer. Moreover, the focal adhesion             kinase (FAK) pathway and the expression of intercellular adhesion molecule‑1 (ICAM‑1)             and vascular cell adhesion molecule‑1 (VCAM‑1) were detected to explore the mechanisms             of SphK1 action. In this study, the expression of SphK1, FAK and phospho-FAK (p-FAK)             was analyzed in 66 surgical specimens of primary colon cancer and matched adjacent             normal tissues by immunohistochemistry and western blotting. In addition, N,N-dimethylsphingosine             (DMS), SphK1 DNA and shRNA transfection were used to regulate the expression and             activity of SphK1 in the LOVO colon cancer cell line. Tumor cell phenotypic changes             were analyzed by cell viability, invasion and apoptosis assays. Results showed             that the expression of SphK1, FAK and p-FAK in colon cancer tissues were significantly             stronger compared to those in matched normal tissues. There was a close correlation             between the expression of SphK1 and FAK or p-FAK and the co-expression of SphK1,             FAK and p-FAK significantly associated with histological grade, Dukes' stage,             lymph node metastasis and distant metastasis. Overexpression of SphK1 after DNA             transfection enhanced tumor cell viability and invasiveness, but suppressed cell             apoptosis. In contrast, suppression of SphK1 by DMS and shRNA reduced tumor cell             viability and invasiveness, but promoted cell apoptosis. The expression of FAK,             p-FAK, ICAM-1 and VCAM-1 in LOVO cells were increased with the overexpression             of SphK1 but decreased with the suppression of SphK1. These findings indicate             that SphK1 regulates tumor cell proliferation, apoptosis and invasion, which ultimately             contributes to tumor progression and malignancy phenotype in colon cancer. FAK             pathway, ICAM-1 and VCAM-1 may play critical roles in this SphK1‑mediated effect.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of                     Guangxi Medical University, Nanning, Guangxi Autonomous Region 530021,                     P.R. China.
authors.forename: Shi-Quan
authors.initials: SQ
authors.lastname: Liu
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Su
authors.forename: Meng-Bin
authors.initials: MB
authors.lastname: Qin
authors.forename: Ye-Bo
authors.initials: YB
authors.lastname: Mao
authors.forename: Jie-An
authors.initials: JA
authors.lastname: Huang
authors.forename: Guo-Du
authors.initials: GD
authors.lastname: Tang
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D018799:Intercellular Adhesion Molecule-1; D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1; D000099157:Sphingosine Kinase; C573420:ICAM1 protein, human