Sujata Jana, Sandipan Brahma, Sonali Arora, Cynthia L Wladyka, Patrick Hoang, Steven Blinka, Rowan Hough, Jessie L Horn, Yuzhen Liu, Li-Jie Wang, Philippe Depeille, Eric Smith, Robert B Montgomery, John K Lee, Michael C Haffner, Funda Vakar-Lopez, Petros Grivas, Jonathan L Wright, Hung-Ming Lam, Peter C Black, Jeroen P Roose, Alexey G Ryazanov, Arvind R Subramaniam, Steven Henikoff, Andrew C Hsieh
We uncover a tumor-suppressive process in urothelium called transcriptional-translational conflict caused by deregulation of the central chromatin remodeling component ARID1A. Loss of Arid1a triggers an increase in a nexus of pro-proliferation transcripts, but a simultaneous inhibition of the eukaryotic elongation factor 2 (eEF2), which results in tumor suppression. Resolution of this conflict through enhancing translation elongation speed enables the efficient and precise synthesis of a network of poised mRNAs resulting in uncontrolled proliferation, clonogenic growth, and bladder cancer progression...
April 13, 2023: Cancer Cell