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学科主题: 临床医学
题名:
Inhibition of sphingosine-1-phosphate phosphatase 1 promotes cancer cells migration in gastric cancer: Clinical implications
作者: Gao, Xiang Y.1,2,3; Li, Lin1,2; Wang, Xiao H.1,2; Wen, Xian Z.1,2; Ji, Ke3; Ye, Lin3; Cai, Jun3; Jiang, Wen G.3; Ji, Jia F.1,2
关键词: sphingosine-1-phosphate phosphatase 1 ; SGPP1 ; gastric cancer ; migration ; invasion
刊名: ONCOLOGY REPORTS
发表日期: 2015-10-01
DOI: 10.3892/or.2015.4162
卷: 34, 期:4, 页:1977-1987
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: PHASE-III TRIAL ; SPHINGOSINE 1-PHOSPHATE ; BREAST-CANCER ; CHEMOTHERAPY ; PHOSPHOHYDROLASE ; EXPRESSION ; STRATEGIES ; SURGERY ; PROTEIN ; STRESS
英文摘要:

Sphingosine-1-phosphate (S1P) plays an important role in regulating many biological processes. Sphingosine-1-phosphate phosphatase 1 (SGPP1) can dephosphorylate S1P into sphingosine and tip the balance of sphingosine-S1P. Increased levels of sphingosine leads to a decrease in the ability of cell invasion as well as an increase in the ability of cell apoptosis. However, little is known regarding the effects of SGPP1 in gastric cancer. The present study examined the function of SGPP1 on gastric cancer cell lines as well as its clinical relevance in gastric cancer progression. Using immunohistochemistry and RT-qPCR techniques, the clinical significance of SGPP1 expression was analyzed in 288 paraffin-embedded gastric tissue specimens and 219 fresh gastric tissues, respectively. Transgenes encoding ribozymes to specifically target human SGPP1 (pEF-SGPP1) was constructed. Human gastric cancer cell lines (AGS and HGC27) were transfected with pEF-SGPP1 transgene and examined by functional analysis. SGPP1 was downregulated in gastric cancer tissues, compared with adjacent normal gastric tissues (p=0.034). SGPP1 mRNA levels in gastric cancer tissues were significantly decreased when compared with their adjacent non-cancerous tissues (p<0.001). Weakly expressed SGPP1 was positively correlated with the lymph node metastasis (p=0.005) and distant metastasis (p=0.031). Kaplan-Meier survival curves revealed that patients with SGPP1 positive expression had a significant increase in overall survival (OS) (p=0.034) and progression-free survival (PFS) (p=0.041). Multivariate analysis indicated the expression of SGPPI was an independent prognostic factor in gastric cancer patients (p=0.041). In vitro experiments showed that knockdown of SGPP1 resulted in an increase in the invasion (2-fold) and migration (5-fold) of AGS and HGC27. The two gastric cancer cells transfected with pEF-SGPP1 exhibited a slower rate of growth with less adhesion. Thus, our findings provided evidence that SGPPI may serve as a prognostic biomarker for patients with advanced gastric cancers.

语种: 英语
所属项目编号: D141100000414002 ; 81374016
项目资助者: Cancer Research Wales ; Albert Hung Foundation ; Yiling Foundation ; Ser Cymru Welsh Life Science Network ; Beijing Municipal Science &amp ; Technology Commission ; Natural Science Foundation of China ; Cardiff University China Medical Scholarship
WOS记录号: WOS:000361159600037
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68003
Appears in Collections:北京大学临床肿瘤学院_胃肠肿瘤中心_期刊论文

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作者单位: 1.Peking Univ, Canc Hosp & Inst, Dept Gastrointestinal Surg, Beijing Canc Hosp, Beijing 100142, Peoples R China
2.Peking Univ, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China
3.Cardiff Univ, Sch Med, Cardiff China Med Res Collaborat, Cardiff CF14 4XN, S Glam, Wales

Recommended Citation:
Gao, Xiang Y.,Li, Lin,Wang, Xiao H.,et al. Inhibition of sphingosine-1-phosphate phosphatase 1 promotes cancer cells migration in gastric cancer: Clinical implications[J]. ONCOLOGY REPORTS,2015,34(4):1977-1987.
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