Altered Expression of Sphingosine-1-Phosphate Metabolizing Enzymes in Oral Cancer Correlate With Clinicopathological Attributes

Vishwakarma, Supriya; Agarwal, Rahul; Goel, Sudhir K.; Panday, Rajendra Kumar; Singh, Rajeev Kumar; Sukumaran, Ravi; Khare, Sarita; Kumar, Ashok

doi:10.1080/07357907.2016.1272695

Cited by 24 publications

(26 citation statements)

References 56 publications

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“…Recently (Vishwakarma et al . ) also showed that in patients with oral squamous cell carcinoma, the S1P phosphatases and sphingosine kinases were differentially regulated in tumors and tumor metastasis. There are conflicting reports on the role of SphK1 in inflammation.…”

Section: Discussionmentioning

confidence: 87%

Alteration of sphingolipid metabolism as a putative mechanism underlying LPS‐induced BBB disruption

Vutukuri

Brunkhorst

Kestner

et al. 2017

Journal of Neurochemistry

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Septic encephalopathy with confusion and agitation occurs early during sepsis and contributes to the severity of the disease. A decrease in the sphingosine-1-phosphate (S1P) blood levels has been shown in patients and in animal models of sepsis. The lipid mediator S1P is known to be involved in endothelial barrier function in a context-dependent manner. We utilized lipopolysaccharide (LPS)-injected mice as a model for septic encephalopathy and first performed tracer permeability assays to assess the blood-brain barrier (BBB) breakdown in vivo. At time points corresponding to the BBB breakdown post LPS injection, we aimed to characterize the regulation of the sphingolipid signaling pathway at the BBB during sepsis. We measured sphingolipid concentrations in blood, in mouse brain microvessels (MBMVs), and brain tissue. We also analyzed the expression of S1P receptors, transporters, and metabolizing enzymes in MBMVs and brain tissue. Primary mouse brain microvascular endothelial cells (MBMECs) were isolated to evaluate the effects of LPS on transendothelial electrical resistance (TEER) as a measure of permeability in vitro. We observed a relevant decrease in S1P levels after LPS injection in all three compartments (blood, MBMVs, brain tissue) that was accompanied by an increased expression of the S1P receptor type 1 and of sphingosine kinase 1 on one hand and of the S1P degrading enzymes lipid phosphate phosphatase 1 (LPP1) and S1P phosphatase 1 on the other hand, as well as a down-regulation of sphingosine kinase 2. Application of LPS to a monolayer of primary MBMECs did not alter TEER, but serum from LPS-treated mice lead to a breakdown of the barrier compared to serum from vehicle-treated mice. We observed profound alterations of the sphingolipid metabolism at the BBB after LPS injection that point toward a therapeutic potential of drugs interfering with this pathway as novel approach for the detrimental overwhelming immune response in sepsis. Read the Editorial Highlight for this article on page 115. Cover Image for this Issue: doi. 10.1111/jnc.14161.

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Section: Discussionmentioning

confidence: 87%

Alteration of sphingolipid metabolism as a putative mechanism underlying LPS‐induced BBB disruption

Vutukuri

Brunkhorst

Kestner

et al. 2017

Journal of Neurochemistry

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“…Flanagan et al reported that downregulating PLPP2 transcriptionally repressed by p53 impaired anchorage-dependent growth of cancer cell lines MCF7, SK-LMS1, MG63, and U2OS, as well as decreased cell proliferation by delaying entry into the S phase of the cell cycle [18]. In addition, it has been demonstrated that PLPP3 was downregulated in approximately 70% of oral squamous cell carcinoma (OSCC) patients, and low expression of PLPP3 positively correlated with TNM stage in OSCC patients [7]. These studies indicated that although belonging to a phosphatidate phosphatase family, different members of the PLPP family function as an oncogene or tumor suppressor in different tumor types.…”

Section: Discussionmentioning

confidence: 99%

“…For example, through analyzing a comparative genomic hybridization array and expression profiling data for a series of 152 ductal breast cancer tissues and 21 breast cancer cell lines, Bernard-Pierrot and colleagues reported that PLPP5 was overexpressed, which contributed to cell survival and cell transformation. Importantly, the oncogenic properties of PLPP5 were further demonstrated by its ability to transform NIH-3 T3 fibroblasts, further inducing their anchorage-independent growth [6]; in oral squamous cell carcinoma (OSCC) patients, PLPP3 was downregulated in approximately 70% OSCC patients and PLPP3 expression negatively correlated with TNM stage and tumor volume [7]. Moreover, Mahmood et al reported that overexpression of PLPP5 caused by amplification of the 8p11-12 chromosomal region, a common genetic event in many epithelial cancers, was found in several cancers, including breast cancer, pancreatic adenocarcinomas and lung carcinoma [8].…”

Section: Introductionmentioning

confidence: 99%

Phospholipid Phosphatase 4 promotes proliferation and tumorigenesis, and activates Ca2+-permeable Cationic Channel in lung carcinoma cells

Zhang

Lin

et al. 2017

Mol Cancer

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BackgroundPhospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma.MethodsPLPP4 expression was examined in 8 paired lung carcinoma tissues by real-time PCR and in 265 lung carcinoma tissues by immunohistochemistry (IHC). Statistical analysis was performed to evaluate the clinical correlation between PLPP4 expression and clinicopathological features and survival in lung carcinoma patients. In vitro and in vivo assays were performed to assess the biological roles of PLPP4 in lung carcinoma. Fluorescence-activated cell sorting, Western blotting and luciferase assays were used to identify the underlying pathway through which PLPP4 silencing mediates biological roles in lung carcinoma.ResultsPLPP4 is differentially elevated in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQC) tissues. Statistical analysis demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade, T category and stage, and poor overall and progression-free survival in lung carcinoma patients. Silencing PLPP4 inhibits proliferation and cell cycle progression in vitro and tumorigenesis in vivo in lung carcinoma cells. Our results further reveal that PLPP4 silencing inhibits Ca2+-permeable cationic channel, suggesting that downregulation of PLPP4 inhibits proliferation and tumorigenesis in lung carcinoma cells via reducing the influx of intracellular Ca2+.ConclusionOur results indicate that PLPP4 may hold promise as a novel marker for the diagnosis of lung carcinoma and as a potential therapeutic target to facilitate the development of novel treatment for lung carcinoma.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0717-5) contains supplementary material, which is available to authorized users.

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“…Downregulation of SPL expression has also been reported in prostate cancer and oral squamous cell carcinoma (OSCC) [ 74 , 76 ]. In contrast, upregulation of SGPL1 mRNA has been reported in OSCC, hepatocellular carcinoma, and ovarian cancer [ 77 – 79 ]. The etiology of this finding and its impact on carcinogenesis remain to be clarified.…”

Section: Structure and Functions Of Splmentioning

confidence: 99%

S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

Kumar

Zamora-Pineda

Degagné

et al. 2017

Mediators of Inflammation

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Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes.

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Altered Expression of Sphingosine-1-Phosphate Metabolizing Enzymes in Oral Cancer Correlate With Clinicopathological Attributes

Cited by 24 publications

References 56 publications

Alteration of sphingolipid metabolism as a putative mechanism underlying LPS‐induced BBB disruption

Alteration of sphingolipid metabolism as a putative mechanism underlying LPS‐induced BBB disruption

Phospholipid Phosphatase 4 promotes proliferation and tumorigenesis, and activates Ca2+-permeable Cationic Channel in lung carcinoma cells

S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

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