sphingosine-kinase and Salivary-Gland-Neoplasms

The progression of salivary adenoid cystic carcinoma (SACC) is closely related to abnormal gene expression. Herein, the role of Sphk1 in SACC was explored. Sphk1 was overexpressed in SACC tissues. In SACC cell lines, Sphk1 induced cell proliferation, inhibited apoptosis, and promoted cell migration. Moreover, Sphk1 overexpression induced up-regulation of the PI3K protein level and AKT phosphorylation level. Rescue assays further showed that activation of the Sphk1 /PI3K/Akt pathway affected various biological functions of SACC cells. Together, these findings suggested that Sphk1 promotes salivary tumorigenesis by activating the PI3K/ Akt pathway, which may provide novel intervention targets for SACC treatment.

Topics: Apoptosis; Carcinoma, Adenoid Cystic; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Phosphatidylinositol 3-Kinase; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Proto-Oncogene Proteins c-akt; Salivary Gland Neoplasms; Signal Transduction

Overexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers. The current study was to characterize the expression of SPHK1 in salivary gland carcinomas (SGC) and to investigate the association between SPHK1 expression and progression of SGC.. The expression of SPHK1 was examined in 2 normal salivary gland tissues, 8 SGC tissues of various clinical stages, and 5 pairs of primary SGC and adjacent salivary gland tissues from the same patient, using real-time PCR and western blot analysis. Furthermore, the SPHK1 protein expression was analyzed in 159 clinicopathologically characterized SGC cases by immunohistochemistry. Statistical analyses were performed to determine the prognostic and diagnostic associations.. SPHK1 expression was found to be markedly upregulated in SGC tissues than that in the normal salivary gland tissues and paired adjacent salivary gland tissues, at both mRNA and protein levels. Statistical analysis revealed a significant correlation of SPHK1 expression with the clinical stage (P = 0.005), T classification (P = 0.017), N classification (P = 0.009), M classification (P = 0.002), and pathological differentiation (P = 0.013). Patients with higher SPHK1 expression had shorter overall survival time, whereas patients with lower SPHK1 expression had better survival. Importantly, patients in the group without adjuvant therapy who exhibited high SPHK1 expression had significantly lower overall survival rates compared with those with low SPHK1 expression. Moreover, multivariate analysis suggested that SPHK1 expression might be an independent prognostic indicator for the survival of SGC patients.. Our results suggest that SPHK1 expression is associated with SGC progression, and might represent as a novel and valuable predictor for adjuvant therapy to SGC patients.

Topics: Adenocarcinoma, Papillary; Biomarkers, Tumor; Blotting, Western; Carcinoma, Acinar Cell; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Cohort Studies; Disease Progression; Female; Gamma Rays; Humans; Immunoenzyme Techniques; Male; Middle Aged; Mucoepidermoid Tumor; Palliative Care; Phosphotransferases (Alcohol Group Acceptor); Prognosis; Radiotherapy, Adjuvant; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salivary Gland Neoplasms; Salivary Glands; Survival Rate