Induction of p53‐mediated transcription and apoptosis by exportin‐1 (XPO1) inhibition in mantle cell lymphoma

• DOI: 10.1111/cas.12430
• Publication Date: 2014-04-26T04:59:20Z
• Authors: Mariko Yoshimura; Jo Ishizawa; Vivian Ruvolo; Archana Dilip; Alfonso Quintás‐C...; Timothy J. McDonnell; Sattva S. Neelapu; Larry W. Kwak; Sharon Shacham; Michael Kauffman; Yoko Tabe; Masako Yokoo; Shinya Kimura; Michael Andreeff; Kensuke Kojima
• Keywords: Transcription

The nuclear transporter exportin‐1 ( XPO 1) is highly expressed in mantle cell lymphoma MCL ) cells, and believed to be associated with the pathogenesis of this disease. 1‐selective inhibitors export SINE compounds have been shown induce apoptosis cells. Given that p53 a cargo protein 1, we sought determine significance activation through 1 inhibition ‐induced We investigated prognostic impact expression cells using Oncomine analysis. mutational/functional status on sensitivity models primary samples, functional role p53‐mediated signaling, were also examined. Increased was poor prognosis patients. inhibitor KPT ‐185 induced p53‐dependent ‐independent mechanisms, critical determinant its induction. ‐185‐induced, occurred transcription‐dependent manner. Exportin‐1 appears influence patient survival , antagonist effectively activates transcription apoptosis, which would provide novel strategy for therapy .