Advani Rahul, Luzzi Sara, Scott Emma, Dalgliesh Caroline, Weischenfeldt Joachim, Munkley Jennifer, Elliott David J
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.
Oncogene. 2023 Oct;42(43):3161-3168. doi: 10.1038/s41388-023-02838-9. Epub 2023 Sep 26.
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.
前列腺癌的进展与传统癌基因和肿瘤抑制因子的活性相关，并受循环甾体激素驱动。一个关键问题是如何识别和治疗快速发展的前列腺肿瘤。在此，我们讨论了剪接调节因子ESRP1和ESRP2的表达，以及它们作为上皮剪接模式“主谋”的作用，是如何被确定为侵袭性增殖前列腺原发性肿瘤的标志物的。我们认为，前列腺癌起源于上皮细胞，以及ESRP1和ESRP2表达随后与更具侵袭性的疾病进展相关联，这将ESRP1和ESRP2确定为谱系存活癌基因。为了推动该领域未来的发展，识别由ESRP1/2控制的调节前列腺癌增殖的基因表达靶点将很重要。未来可能设计出针对侵袭性前列腺肿瘤中ESRP1和ESRP2蛋白活性或其调控的剪接异构体的疗法。这些疗法的设计可能因产生更易促进肿瘤转移的间充质剪接环境的风险而变得复杂。
