ArticleJournal of translational medicine2011
An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma.
Article in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 3 of them syntheses that pooled it.
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Who cites it
45 citing papers in PubMed, 3 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Increased Sphingosine Kinase 1 Expression Is Associated with Poor Prognosis in Human Solid Tumors: A Meta-Analysis.Disease markers · 2022Pooled it
- Ranking candidate genes of esophageal squamous cell carcinomas based on differentially expressed genes and the topological properties of the co-expression network.European journal of medical research · 2014Pooled it
- Pooled it
- Mediation of sphingolipid metabolism on the relationship between human nitrosamines exposure and esophageal cancer risk.Scientific reports · 2026Article
- Sphingolipid metabolism-related genes B4GALNT1 and CERS4 as prognostic biomarkers in lung adenocarcinoma.PloS one · 2026Article
- Sphingolipid modulation and anti-tumor activity of Jaspine B in HepG2 bearing mice.Archives of pharmacal research · 2025Article
- Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer.Journal of cellular and molecular medicine · 2025Article
- SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation.Discover oncology · 2024Article
- The role of ACER2 in intestinal sphingolipid metabolism and gastrointestinal cancers.Frontiers in immunology · 2024Review
- HOXC11 drives lung adenocarcinoma progression through transcriptional regulation of SPHK1.Cell death & disease · 2023Article
- Effects of adipocyte-conditioned cell culture media on S1P treatment of human triple-negative breast cancer cells.PloS one · 2023Article
- Review
- The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Frontiers in oncology · 2022Review
- PCBP1 regulates the transcription and alternative splicing of metastasis‑related genes and pathways in hepatocellular carcinoma.Scientific reports · 2021Article
- Review
- SGPL1Cancer gene therapy · 2020Article
- Upregulation of sphingosine kinase 1 is associated with recurrence and poor prognosis in papillary thyroid carcinoma.Oncology letters · 2019Article
- Prognostic roles of the expression of sphingosine-1-phosphate metabolism enzymes in non-small cell lung cancer.Translational lung cancer research · 2019Article
- SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo.EBioMedicine · 2019Article
- Sphingosine Kinase 1 Signaling Promotes Metastasis of Triple-Negative Breast Cancer.Cancer research · 2019Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo.
methodsA metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting.
resultsWe identified sphingosine kinase 1 (SPHK1) as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P < 0.0001) and lymph node metastasis (P = 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P < 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR.
conclusionIn summary, our data implicate SPHK1 in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.
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