journal contribution
posted on 2023-03-31, 01:00 authored by Tomasz B. Owczarek, Takashi Kobayashi, Ricardo Ramirez, Lijie Rong, Anna M. Puzio-Kuter, Gopa Iyer, Min Yuen Teo, Francisco Sánchez-Vega, Jingqiang Wang, Nikolaus Schultz, Tian Zheng, David B. Solit, Hikmat A. Al-Ahmadie, Cory Abate-Shen Supplementary Data from ARF Confers a Context-Dependent Response to Chemotherapy in Muscle-Invasive Bladder Cancer
Funding
NIH
NCI
Bladder Cancer Advocacy Network
American Cancer Society Research
History
ARTICLE 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.
