Prostate cancer progression is connected to the activity of conventional oncogenes and tumour suppressors and driven by circulating steroid hormones. A key issue has been how to identify and care for aggressively developing prostate tumours. Here we discuss how expression of the splicing regulators ESRP1 and ESRP2, and how their role as "masterminds" of epithelial splicing patterns, have been identified as markers of aggressively proliferating prostate primary tumours. We suggest that the origin of prostate cancer within epithelial cells, and the subsequent association of ESRP1 and ESRP2 expression with more aggressive disease progression, identify ESRP1 and ESRP2 as lineage survival oncogenes. To move this field on in the future it will be important to identify the gene expression targets controlled by ESRP1/2 that regulate prostate cancer proliferation. Potential future therapies could be designed to target ESRP1 and ESRP2 protein activity or their regulated splice isoforms in aggressive prostate tumours. Design of these therapies is potentially complicated by the risk of producing a more mesenchymal splicing environment that might promote tumour metastasis.
Oncogene. 2023 Sep 26 [Epub ahead of print]
Rahul Advani, Sara Luzzi, Emma Scott, Caroline Dalgliesh, Joachim Weischenfeldt, Jennifer Munkley, David J Elliott
Newcastle University Biosciences Institute (NUBI) and Newcastle University Cancer Centre, Newcastle University, Newcastle Upon Tyne, NE1 3BZ, United Kingdom., Biotech Research & Innovation Centre (BRIC), The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Newcastle University Biosciences Institute (NUBI) and Newcastle University Cancer Centre, Newcastle University, Newcastle Upon Tyne, NE1 3BZ, United Kingdom. .