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000277470 1001_ $$00000-0001-6903-3001$$aAlborzinia, Hamed$$b0$$eFirst author
000277470 245__ $$aLRP8-mediated selenocysteine uptake is a targetable vulnerability in MYCN-amplified neuroblastoma.
000277470 260__ $$aHeidelberg$$bEMBO Press$$c2023
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000277470 500__ $$a#EA:A010#LA:A010# / 2023 Aug 7;15(8):e18014
000277470 520__ $$aFerroptosis has emerged as an attractive strategy in cancer therapy. Understanding the operational networks regulating ferroptosis may unravel vulnerabilities that could be harnessed for therapeutic benefit. Using CRISPR-activation screens in ferroptosis hypersensitive cells, we identify the selenoprotein P (SELENOP) receptor, LRP8, as a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis. Genetic deletion of LRP8 leads to ferroptosis as a result of an insufficient supply of selenocysteine, which is required for the translation of the antiferroptotic selenoprotein GPX4. This dependency is caused by low expression of alternative selenium uptake pathways such as system Xc- . The identification of LRP8 as a specific vulnerability of MYCN-amplified neuroblastoma cells was confirmed in constitutive and inducible LRP8 knockout orthotopic xenografts. These findings disclose a yet-unaccounted mechanism of selective ferroptosis induction that might be explored as a therapeutic strategy for high-risk neuroblastoma and potentially other MYCN-amplified entities.
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000277470 650_7 $$2Other$$aferroptosis
000277470 650_7 $$2Other$$aneuroblastoma
000277470 650_7 $$2Other$$aselenocysteine
000277470 650_7 $$2Other$$aselenoprotein
000277470 650_7 $$2Other$$asynthetic lethality
000277470 7001_ $$00009-0006-8826-647X$$aChen, Zhiyi$$b1
000277470 7001_ $$0P:(DE-He78)ec0580bc220c5df0a90acb9e472f922d$$aYildiz, Umut$$b2$$eFirst author
000277470 7001_ $$00000-0002-0369-4488$$aFreitas, Florencio Porto$$b3
000277470 7001_ $$0P:(DE-He78)38900a0e1ae96a725db546cb7b909adb$$aVogel, Felix Christian Eduard$$b4$$udkfz
000277470 7001_ $$0P:(DE-He78)fe6756f3b8b09aacf42ed15b65448146$$aVarga, Julianna Patricia$$b5
000277470 7001_ $$aBatani, Jasmin$$b6
000277470 7001_ $$aBartenhagen, Christoph$$b7
000277470 7001_ $$00000-0003-0485-7303$$aSchmitz, Werner$$b8
000277470 7001_ $$aBüchel, Gabriele$$b9
000277470 7001_ $$00000-0001-6376-2588$$aMichalke, Bernhard$$b10
000277470 7001_ $$00000-0002-5387-1358$$aZheng, Jashuo$$b11
000277470 7001_ $$aMeierjohann, Svenja$$b12
000277470 7001_ $$aGirardi, Enrico$$b13
000277470 7001_ $$00000-0002-0690-9878$$aEspinet, Elisa$$b14
000277470 7001_ $$aFlórez, Andrés F$$b15
000277470 7001_ $$aDos Santos, Ancely Ferreira$$b16
000277470 7001_ $$0P:(DE-He78)f086a8a0e493edd2642811ac3248b65b$$aAroua, Nesrine$$b17$$udkfz
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000277470 7001_ $$0P:(DE-He78)7a79c093c80aef7d52198fbb23b0f2e5$$aHaenlin, Julie$$b19$$udkfz
000277470 7001_ $$0P:(DE-He78)e52c8f6ae826320eaf2fb173e162070d$$aSchlicker, Lisa$$b20$$udkfz
000277470 7001_ $$00000-0001-5236-8470$$aXavier da Silva, Thamara N$$b21
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000277470 7001_ $$aSuperti-Furga, Giulio$$b24
000277470 7001_ $$00000-0002-0376-6533$$aEilers, Martin$$b25
000277470 7001_ $$00000-0003-1140-5612$$aConrad, Marcus$$b26
000277470 7001_ $$00000-0002-4360-6809$$aFabiano, Marietta$$b27
000277470 7001_ $$00000-0003-1380-4780$$aSchweizer, Ulrich$$b28
000277470 7001_ $$00000-0003-1363-1242$$aFischer, Matthias$$b29
000277470 7001_ $$0P:(DE-He78)94ae391f53fb9285e1b68f9930615af1$$aSchulze, Almut$$b30$$udkfz
000277470 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b31$$eLast author$$udkfz
000277470 7001_ $$00000-0001-7706-1379$$aFriedmann Angeli, José Pedro$$b32
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