TY  - JOUR
AU  - Georgilis, Athena
AU  - Klotz, Sabrina
AU  - Hanley, Christopher J
AU  - Herranz, Nicolas
AU  - Weirich, Benedikt
AU  - Morancho, Beatriz
AU  - Leote, Ana Carolina
AU  - D'Artista, Luana
AU  - Gallage, Suchira
AU  - Seehawer, Marco
AU  - Carroll, Thomas
AU  - Dharmalingam, Gopuraja
AU  - Wee, Keng Boon
AU  - Mellone, Marco
AU  - Pombo, Joaquim
AU  - Heide, Danijela
AU  - Guccione, Ernesto
AU  - Arribas, Joaquín
AU  - Barbosa-Morais, Nuno L
AU  - Heikenwalder, Mathias
AU  - Thomas, Gareth J
AU  - Zender, Lars
AU  - Gil, Jesús
TI  - PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells.
JO  - Cancer cell
VL  - 34
IS  - 1
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2018-01158
SP  - 85 - 102.e9
PY  - 2018
AB  - Oncogene-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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29990503
C2  - pmc:PMC6048363
DO  - DOI:10.1016/j.ccell.2018.06.007
UR  - https://inrepo02.dkfz.de/record/136720
ER  -