SRP19 and the protein secretion machinery is a targetable vulnerability in cancers with APC loss
Xi, X.; Liu, L.; Tuano, N.; Tailhades, J.; Mouradov, D.; Sieber, O.; Cryle, M.; Segelov, E.; Rosenbluh, J.
Show abstract
Adenomatous Polyposis Coli (APC) is a tumour suppressor that is frequently lost in colorectal and other cancers. A common mechanism for APC loss includes heterozygous APC deletion. Here, we show that SRP19, is located near APC and is often co-deleted in these tumours. Heterozygous APC/SRP19 loss leads to lower levels of SRP19 mRNA and protein. Consequently, cells with APC/SRP19 loss are vulnerable to partial suppression of SRP19. We show that SRP19 loss is a unique vulnerability since SRP19 is rate limiting for the formation of the Signal Recognition Particle (SRP), a complex that mediates translocation of proteins to the ER. Consistent with these observations, partial SRP19 knock-down or low dose Arsenic Trioxide treatment induces ER stress and inhibits proliferation in APC/SRP19 loss cancers. Our work identifies a new strategy to treat cancers with APC/SRP19 heterozygous deletions and provides a framework for identifying vulnerabilities associated with loss of a tumour suppressor.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Oncogenic YAP mediates changes in chromatin accessibility and activity that drive cell cycle gene expression and cell migration 96%
- CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex 96%
- Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress 96%
Similar papers in this journal
- IGF targeting perturbs global replication through ribonucleotide reductase dysfunction 95%
- Germline and somatic genetic variants in the p53 pathway interact to affect cancer risk, progression and drug response 95%
- Leveraging Allele-Specific Expression for Therapeutic Response Gene Discovery in Glioblastoma. 95%
Similar papers in this journal
Similar papers in this journal
- Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A 96%
- KSR1-and ERK-dependent Translational Regulation of the Epithelial-to-Mesenchymal Transition 96%
- Chemotherapy resistance due to epithelial-to-mesenchymal transition is caused by abnormal lipid metabolic balance 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.