| First Author | Jana S | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 5 | Pages | 853-870.e13 |
| PubMed ID | 37084735 | Mgi Jnum | J:373707 |
| Mgi Id | MGI:8255606 | Doi | 10.1016/j.ccell.2023.03.021 |
| Citation | Jana S, et al. (2023) Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression. Cancer Cell 41(5):853-870.e13 |
| abstractText | 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. We observe a similar phenomenon in patients with ARID1A-low tumors, which also exhibit increased translation elongation activity through eEF2. These findings have important clinical implications because ARID1A-deficient, but not ARID1A-proficient, tumors are sensitive to pharmacologic inhibition of protein synthesis. These discoveries reveal an oncogenic stress created by transcriptional-translational conflict and provide a unified gene expression model that unveils the importance of the crosstalk between transcription and translation in promoting cancer. |
