ArticleClinical and translational gastroenterology2014
Sphingosine kinase 1 promotes malignant progression in colon cancer and independently predicts survival of patients with colon cancer by competing risk approach in South asian population.
Article in Clinical and translational gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells.International journal of molecular sciences · 2023Article
- Sphingosine 1-phosphate lyase facilitates cancer progression through converting sphingolipids to glycerophospholipids.Clinical and translational medicine · 2022Article
- Differential Expression of the Sphingolipid Pathway Is Associated with Sensitivity to the PP2A Activator FTY720 in Colorectal Cancer Cell Lines.Journal of clinical medicine · 2021Article
- Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells.Frontiers in molecular biosciences · 2021Review
- Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.Cancer medicine · 2020Review
- Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer.Molecules (Basel, Switzerland) · 2020Review
- Resistance of melanoma to immune checkpoint inhibitors is overcome by targeting the sphingosine kinase-1.Nature communications · 2020Article
- Colon Cancer and Perturbations of the Sphingolipid Metabolism.International journal of molecular sciences · 2019Review
- Sphingolipids and their metabolism in physiology and disease.Nature reviews. Molecular cell biology · 2018Review
- Targeting sphingosine kinase 1 induces MCL1-dependent cell death in acute myeloid leukemia.Blood · 2017Article
- Predictive and prognostic value of sphingosine kinase 1 expression in patients with invasive ductal carcinoma of the breast.American journal of translational research · 2017Article
- S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.Mediators of inflammation · 2017Review
- Role of neutral ceramidase in colon cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography.Journal of cell science · 2016Article
- Overexpression of SphK1 enhances cell proliferation and invasion in triple-negative breast cancer via the PI3K/AKT signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer.World journal of gastroenterology · 2016Article
- Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer.Oncotarget · 2015Article
- Sphingosine Kinase 2 and Ceramide Transport as Key Targets of the Natural Flavonoid Luteolin to Induce Apoptosis in Colon Cancer Cells.PloS one · 2015Article
- [Role of SPHK1 regulates multi-drug resistance of small cell lung cancer and its clinical significance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2014Article
- SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro.
methodsSphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined.
resultsHigh SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU.
conclusionOur findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.