Upregulation of ABC transporters contributes to chemoresistance of sphingosine 1-phosphate lyase-deficient fibroblasts

Ihlefeld, Katja; Vienken, Hans; Claas, Ralf Frederik; Rudowski, Agnes; Braak, Michael ter; Koch, Alexander; Veldhoven, Paul P. Van; Pfeilschifter, Josef; Heringdorf, Dagmar Meyer zu

doi:10.1194/jlr.m052761

Cited by 17 publications

(20 citation statements)

References 41 publications

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“…Interestingly, upregulation of SPL levels by consumption of sphingadienes, plant-type sphingolipids that cannot be converted to S1P, was able to enhance the metabolism of S1P attenuating STAT3 signaling, cytokine production, and tumorigenesis [39]. SPL deficiency or its inhibition has also been associated with elevated nuclear S1P levels and reduced HDAC activity that in turn induced dysregulation of Ca 2+ homoeostasis [40], and upregulation of several S1P transporters, including multi-drug resistant proteins, contributing to chemoresistance [41]. …”

Section: S1p Lyase and S1p Phosphatasesmentioning

confidence: 99%

Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy

Newton

Lima

Maceyka

et al. 2015

Experimental Cell Research

227

198

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Section: S1p Lyase and S1p Phosphatasesmentioning

confidence: 99%

Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy

Newton

Lima

Maceyka

et al. 2015

Experimental Cell Research

227

198

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“…In breast cancer cells, estradiol stimulates SK1 activity and S1P export via both ABCC1 and ABCG2 (Takabe et al ., 2010). In a recent paper, it was shown that S1P transporters including ABCA1, ABCB1, ABCC1 and Spinster 2 (Spns2) are upregulated and can lead to chemoresistance in SPL-deficient mouse embryonic fibroblasts (Ihlefeld et al ., 2015). Interestingly, while these ABC transport proteins can transport S1P out of cells, their downregulation does not decrease the S1P levels in plasma (Lee et al ., 2007).…”

Section: S1p Transportationmentioning

confidence: 99%

Sphingosine-1-phosphate metabolism: A structural perspective

Pulkoski-Gross¹,

Donaldson

Obeid

2015

Critical Reviews in Biochemistry and Molecular Biology

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Sphingolipids represent an important class of bioactive signaling lipids which have key roles in numerous cellular processes. Over the last few decades, the levels of bioactive sphingolipids and/or their metabolizing enzymes have been realized to be important factors involved in disease development and progression, most notably in cancer. Targeting sphingolipid-metabolizing enzymes in disease states has been the focus of many studies and has resulted in a number of pharmacological inhibitors, with some making it into the clinic as therapeutics. In order to better understand the regulation of sphingolipid-metabolizing enzymes as well as to develop much more potent and specific inhibitors, the field of sphingolipids has recently taken a turn toward structural biology. The last decade has seen the structural determination of a number of sphingolipid enzymes and effector proteins. In these terms, one of the most complete arms of the sphingolipid pathway is the sphingosine-1-phosphate (S1P) arm. The structures of proteins involved in the function and regulation of S1P are being used to investigate further the regulation of said proteins as well as in the design and development of inhibitors as potential therapeutics.

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“…Since anthracyclines like DAUN and DOX are substrates for P-gp (P-glycoprotein 1 or ABCB1) [52] some cancer cells express large amounts of P-gp, which would gain anthracycline related resistance [53,54]. Interestingly, it has been demonstrated that curcumin not only interacts directly with the drug binding site of the ABCB1-transporter [55,56] but also the expression of the multidrug resistance gene and ABCB1-transporter (protein) was significantly suppressed in both, in vitro and in vivo, respectively [57].…”

Section: Discussionmentioning

confidence: 99%