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@ARTICLE{Georgilis:136720,
author = {A. Georgilis and S. Klotz and C. J. Hanley and N. Herranz
and B. Weirich$^*$ and B. Morancho and A. C. Leote and L.
D'Artista and S. Gallage$^*$ and M. Seehawer and T. Carroll
and G. Dharmalingam and K. B. Wee and M. Mellone and J.
Pombo and D. Heide$^*$ and E. Guccione and J. Arribas and N.
L. Barbosa-Morais and M. Heikenwalder$^*$ and G. J. Thomas
and L. Zender$^*$ and J. Gil},
title = {{PTBP}1-{M}ediated {A}lternative {S}plicing {R}egulates the
{I}nflammatory {S}ecretome and the {P}ro-tumorigenic
{E}ffects of {S}enescent {C}ells.},
journal = {Cancer cell},
volume = {34},
number = {1},
issn = {1535-6108},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2018-01158},
pages = {85 - 102.e9},
year = {2018},
abstract = {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.},
cin = {F180 / V076 / L801},
ddc = {610},
cid = {I:(DE-He78)F180-20160331 / I:(DE-He78)V076-20160331 /
I:(DE-He78)L801-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29990503},
pmc = {pmc:PMC6048363},
doi = {10.1016/j.ccell.2018.06.007},
url = {https://inrepo02.dkfz.de/record/136720},
}