Abstract：
:Muscle-invasive bladder cancer (MIBC) generally responds poorly to treatment and tends to exhibit significant mortality. Here we show that expression of the tumor suppressor p14ARF (ARF) is upregulated in aggressive subtypes of MIBC. Accumulation of ARF in the nucleolus is associated with poor outcome and attenuated response to chemotherapy. In both genetically engineered mouse models and murine xenograft models of human MIBC, we demonstrate that tumors expressing ARF failed to respond to treatment with the platinum-based chemotherapy agent cisplatin. Resistance was mediated in part by the integrin-binding protein ITGB3BP (CENPR) and reflected ARF-dependent impairment of protein translation, which was exaggerated by drug treatment. Overall, our results highlight a context-dependent role for ARF in modulating the drug response of bladder cancer. Cancer Res; 77(4); 1035-46. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Owczarek TB,Kobayashi T,Ramirez R,Rong L,Puzio-Kuter AM,Iyer G,Teo MY,Sánchez-Vega F,Wang J,Schultz N,Zheng T,Solit DB,Al-Ahmadie HA,Abate-Shen Cdoi
10.1158/0008-5472.CAN-16-2621subject
Has Abstractpub_date
2017-02-15 00:00:00pages
1035-1046issue
4eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-2621journal_volume
77pub_type
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