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000136720 0247_ $$2doi$$a10.1016/j.ccell.2018.06.007
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000136720 0247_ $$2ISSN$$a1878-3686
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000136720 041__ $$aeng
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000136720 1001_ $$aGeorgilis, Athena$$b0
000136720 245__ $$aPTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells.
000136720 260__ $$aCambridge, Mass.$$bCell Press$$c2018
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000136720 520__ $$aOncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1. PTBP1 regulates the alternative splicing of genes involved in intracellular trafficking, such as EXOC7, to control the SASP. Inhibition of PTBP1 prevents the pro-tumorigenic effects of the SASP and impairs immune surveillance without increasing the risk of tumorigenesis. In conclusion, our study identifies SASP inhibition as a powerful and safe therapy against inflammation-driven cancer.
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000136720 7001_ $$aKlotz, Sabrina$$b1
000136720 7001_ $$aHanley, Christopher J$$b2
000136720 7001_ $$aHerranz, Nicolas$$b3
000136720 7001_ $$0P:(DE-He78)c9804a143404cd77d42623308f468c87$$aWeirich, Benedikt$$b4$$udkfz
000136720 7001_ $$aMorancho, Beatriz$$b5
000136720 7001_ $$aLeote, Ana Carolina$$b6
000136720 7001_ $$aD'Artista, Luana$$b7
000136720 7001_ $$0P:(DE-HGF)0$$aGallage, Suchira$$b8
000136720 7001_ $$aSeehawer, Marco$$b9
000136720 7001_ $$aCarroll, Thomas$$b10
000136720 7001_ $$aDharmalingam, Gopuraja$$b11
000136720 7001_ $$aWee, Keng Boon$$b12
000136720 7001_ $$aMellone, Marco$$b13
000136720 7001_ $$aPombo, Joaquim$$b14
000136720 7001_ $$0P:(DE-He78)92c93319837b4b915db8393795faf0b6$$aHeide, Danijela$$b15$$udkfz
000136720 7001_ $$aGuccione, Ernesto$$b16
000136720 7001_ $$aArribas, Joaquín$$b17
000136720 7001_ $$aBarbosa-Morais, Nuno L$$b18
000136720 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwalder, Mathias$$b19$$udkfz
000136720 7001_ $$aThomas, Gareth J$$b20
000136720 7001_ $$0P:(DE-He78)1ba2900406378e069d32db376c7818db$$aZender, Lars$$b21$$udkfz
000136720 7001_ $$aGil, Jesús$$b22
000136720 773__ $$0PERI:(DE-600)2074034-7$$a10.1016/j.ccell.2018.06.007$$gVol. 34, no. 1, p. 85 - 102.e9$$n1$$p85 - 102.e9$$tCancer cell$$v34$$x1535-6108$$y2018
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