Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Autonomous Region 530021, P.R. China.
Int J Oncol. 2013 Feb;42(2):617-26. doi: 10.3892/ijo.2012.1733. Epub 2012 Dec 12.
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.
研究表明，在某些类型的人类肿瘤中，鞘氨醇激酶 1（SphK1）具有促进肿瘤的功能，然而，其对结肠癌的影响尚不清楚。本研究旨在探讨 SphK1 在结肠癌进展和肿瘤细胞表型变化中的作用。此外，还检测了粘着斑激酶（FAK）途径以及细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达，以探讨 SphK1 作用的机制。在本研究中，通过免疫组织化学和 Western blot 分析了 66 例原发性结肠癌手术标本及其匹配的相邻正常组织中 SphK1、FAK 和磷酸化 FAK（p-FAK）的表达。此外，还使用 N,N-二甲基鞘氨醇（DMS）、SphK1 DNA 和 shRNA 转染来调节 LOVO 结肠癌细胞系中 SphK1 的表达和活性。通过细胞活力、侵袭和凋亡测定分析肿瘤细胞表型变化。结果表明，与匹配的正常组织相比，结肠癌组织中 SphK1、FAK 和 p-FAK 的表达明显增强。SphK1 的表达与 FAK 或 p-FAK 的表达密切相关，SphK1、FAK 和 p-FAK 的共表达与组织学分级、 Dukes 分期、淋巴结转移和远处转移显著相关。DNA 转染后 SphK1 的过表达增强了肿瘤细胞的活力和侵袭性，但抑制了细胞凋亡。相反，DMS 和 shRNA 抑制 SphK1 降低了肿瘤细胞的活力和侵袭性，但促进了细胞凋亡。LOVO 细胞中 FAK、p-FAK、ICAM-1 和 VCAM-1 的表达随 SphK1 的过表达而增加，随 SphK1 的抑制而减少。这些发现表明，SphK1 调节肿瘤细胞的增殖、凋亡和侵袭，最终促进了结肠癌的肿瘤进展和恶性表型。FAK 途径、ICAM-1 和 VCAM-1 可能在 SphK1 介导的这种效应中发挥关键作用。
Zotero 插件