Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells

Lee, Menq-Jer

doi:10.3892/ijo.2012.1379

Cited by 24 publications

(18 citation statements)

References 32 publications

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“…Interestingly, we found five upregulated cancer-related genes ( Epha3, Hjurp, Kif26, S1pr3 and Pde3B ) that shared miRNAs with the HMGA1P7 transcript. These genes are involved in various human cancers (glioblastoma, breast and hematological cancers), and are candidate therapeutic targets [37-41]. Real-time PCR experiments confirmed upregulation of all these genes in HMGA1P7- MEFs (Supplementary Figure 1).…”

Section: Resultsmentioning

confidence: 99%

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

et al. 2014

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The High Mobility Group A (HMGA) are nuclear proteins that participate in the organization of nucleoprotein complexes involved in chromatin structure, replication and gene transcription. HMGA overexpression is a feature of human cancer and plays a causal role in cell transformation. Since non-coding RNAs and pseudogenes are now recognized to be important in physiology and disease, we investigated HMGA1 pseudogenes in cancer settings using bioinformatics analysis. Here we report the identification and characterization of two HMGA1 non-coding pseudogenes, HMGA1P6 and HMGA1P7. We show that their overexpression increases the levels of HMGA1 and other cancer-related proteins by inhibiting the suppression of their synthesis mediated by microRNAs. Consistently, embryonic fibroblasts from HMGA1P7-overexpressing transgenic mice displayed a higher growth rate and reduced susceptibility to senescence. Moreover, HMGA1P6 and HMGA1P7 were overexpressed in human anaplastic thyroid carcinomas, which are highly aggressive, but not in differentiated papillary carcinomas, which are less aggressive. Lastly, the expression of the HMGA1 pseudogenes was significantly correlated with HMGA1 protein levels thereby implicating HMGA1P overexpression in cancer progression. In conclusion, HMGA1P6 and HMGA1P7 are potential proto-oncogenic competitive endogenous RNAs.

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Section: Resultsmentioning

confidence: 99%

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

et al. 2014

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“…The functions of S1P receptors are under investigation. Some results support that S1P 1 and S1P 3 mediate cell proliferation [43], migration [44, 45], invasion [46, 47], and angiogenesis [48]. …”

Section: Anti-cancer Targets In the Ceramide Signaling Pathwaymentioning

confidence: 98%

A Review of Ceramide Analogs as Potential Anticancer Agents

2013

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Summary Ceramide serves as a central mediator in sphingolipid metabolism and signaling pathways, regulating many fundamental cellular responses. It is referred to as a “tumor suppressor lipid”, since it powerfully potentiates signaling events which drive apoptosis, cell cycle arrest, and autophagic responses. In the typical cancer cell, ceramide levels and signaling are usually suppressed by over-expression of ceramide-metabolizing enzymes or down-regulation of ceramide-generating enzymes. However, chemotherapeutic drugs as well as radiotherapy increase intracellular ceramide levels while exogenously treating cancer cells with short-chain ceramides leads to anti-cancer effects. All evidence currently points to the fact that the up-regulation of ceramide level is a promising anti-cancer target. In this review, we exhibited a full scroll of anti-cancer ceramide analogs as down-stream receptor agonists and ceramide metabolizing enzyme inhibitors.

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“…Both bioactive lipids have been reported to play an important role in development of skeletal muscle (8, 9), and, in addition, S1P has been demonstrated to direct migration of various types of tumor cells (10–12). It is known that S1P is secreted from several types of cells and binds to serum albumin and lipoproteins, all of which explains its relatively high (micromolar) concentration in peripheral blood and lymph (13).…”

Section: Introductionmentioning

confidence: 99%

Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy

Schneider

Bryndza

Abdel‐Latif

et al. 2013

Molecular Cancer Research

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We observed that sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) strongly enhance in vitro motility and adhesion of human rhabdomyosarcoma (RMS) cells. This effect was observed at physiological concentrations of both bioactive lipids, which are present in biological fluids, and is much stronger than the effects observed in response to known RMS pro-metastatic factors such as stromal derived factors-1 (SDF-1) or hepatocyte growth factor/scatter factor (HGF/SF). We also present novel evidence that the levels of S1P and C1P increase in several organs after γ-irradiation or chemotherapy, which indicates induction of an unwanted pro-metastatic environment related to treatment. Most importantly, we found that the metastasis of RMS cells in response to S1P can be effectively inhibited in vivo with the S1P-specific binder NOX-S93 that is based on a high affinity Spiegelmer. We propose that bioactive lipids play a previously underappreciated role in dissemination of RMS and the unwanted side effects of radio/chemotherapy by creating a pro-metastatic microenvironment. Therefore, an anti-metastatic treatment with specific S1P-binding scavenger such as NOX-S93 could become a part of standard radio/chemotherapy.

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Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells

Cited by 24 publications

References 32 publications

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

A Review of Ceramide Analogs as Potential Anticancer Agents

Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy

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