000132455 001__ 132455
000132455 005__ 20240229105017.0
000132455 0247_ $$2doi$$a10.1038/s41419-018-0342-2
000132455 0247_ $$2pmid$$apmid:29463797
000132455 0247_ $$2altmetric$$aaltmetric:33525481
000132455 037__ $$aDKFZ-2018-00143
000132455 041__ $$aeng
000132455 082__ $$a570
000132455 1001_ $$0P:(DE-He78)d861e207ca85f7e171d3225d4a4536cd$$aAnsari, Shariq Suhail$$b0$$eFirst author
000132455 245__ $$aInduction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells.
000132455 260__ $$aLondon [u.a.]$$bNature Publishing Group$$c2018
000132455 3367_ $$2DRIVER$$aarticle
000132455 3367_ $$2DataCite$$aOutput Types/Journal article
000132455 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1659443090_15546
000132455 3367_ $$2BibTeX$$aARTICLE
000132455 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000132455 3367_ $$00$$2EndNote$$aJournal Article
000132455 520__ $$aEndoplasmic reticulum (ER) plays an essential role in cell function and survival. Accumulation of unfolded or misfolded proteins in the lumen of the ER activates the unfolded protein response (UPR), resulting in ER stress and subsequent apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in oral squamous cell carcinoma (OSCC). In the present study, we evaluate erufosine's role to induce ER and mitochondrial stress leading to autophagy, apoptosis, and ROS induction. The cellular toxicity of erufosine was determined in two OSCC cell lines and gene expression and enrichment analyses were performed. A positive enrichment of ER stress upon erufosine exposure was observed, which was verified at protein levels for the ER stress sensors and their downstream mediators. Knockdown and pharmacological inhibition of the ER stress sensors PERK and XBP1 revealed their involvement into erufosine's cellular effects, including proliferation, apoptosis, and autophagy induction. Autophagy was confirmed by increased acidic vacuoles and LC3-B levels. Upon erufosine exposure, calcium influx into the cytoplasm of the two OSCC cell lines was seen. Apoptosis was confirmed by nuclear staining, Annexin-V, and immunoblotting of caspases. The induction of mitochondrial stress upon erufosine exposure was predicted by gene set enrichment analysis (GSEA) and shown by erufosine's effect on mitochondrial membrane potential, ATP, and ROS production in OSCC cells. These data show that ER and mitochondrial targeting by erufosine represents a new facet of its mechanism of action as well as a promising new framework in the treatment of head and neck cancers.
000132455 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0
000132455 588__ $$aDataset connected to CrossRef, PubMed,
000132455 7001_ $$0P:(DE-He78)ef6b064b6d3463cee768ed2e261c10cd$$aSharma, Ashwini Kumar$$b1
000132455 7001_ $$0P:(DE-He78)34d5c41508d3317e721bfb593ef5948d$$aSoni, Himanshu$$b2
000132455 7001_ $$0P:(DE-HGF)0$$aAli, Doaa M$$b3
000132455 7001_ $$0P:(DE-He78)a33ae52a1d80b847405db3ab83b9e90d$$aTews, Björn$$b4
000132455 7001_ $$aKönig, Rainer$$b5
000132455 7001_ $$aEibl, Hansjörg$$b6
000132455 7001_ $$0P:(DE-He78)7e60033e3eaaebb9ba30c905ade4a676$$aBerger, Martin$$b7$$eLast author
000132455 773__ $$0PERI:(DE-600)2541626-1$$a10.1038/s41419-018-0342-2$$gVol. 9, no. 3, p. 296$$n3$$p296$$tCell death & disease$$v9$$x2041-4889$$y2018
000132455 909CO $$ooai:inrepo02.dkfz.de:132455$$pVDB
000132455 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)d861e207ca85f7e171d3225d4a4536cd$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000132455 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ef6b064b6d3463cee768ed2e261c10cd$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000132455 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)34d5c41508d3317e721bfb593ef5948d$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000132455 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000132455 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a33ae52a1d80b847405db3ab83b9e90d$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000132455 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7e60033e3eaaebb9ba30c905ade4a676$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000132455 9131_ $$0G:(DE-HGF)POF3-317$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vTranslational cancer research$$x0
000132455 9141_ $$y2018
000132455 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCELL DEATH DIS : 2015
000132455 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000132455 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000132455 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000132455 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal
000132455 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ
000132455 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ
000132455 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000132455 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000132455 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000132455 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000132455 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000132455 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCELL DEATH DIS : 2015
000132455 9201_ $$0I:(DE-He78)G401-20160331$$kG401$$lMolekulare Toxikologie und Chemotherapie$$x0
000132455 9201_ $$0I:(DE-He78)V077-20160331$$kV077$$lAG Molekulare Mechanismen der Tumorzell-Invasion$$x1
000132455 980__ $$ajournal
000132455 980__ $$aVDB
000132455 980__ $$aI:(DE-He78)G401-20160331
000132455 980__ $$aI:(DE-He78)V077-20160331
000132455 980__ $$aUNRESTRICTED