Silva Karla C S, Tambwe Nadine, Mahfouz Dalia H, Wium Martha, Cacciatore Stefano, Paccez Juliano D, Zerbini Luiz F
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town 7925, South Africa.
Integrative Biomedical Sciences Division, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Genes (Basel). 2024 Apr 2;15(4):450. doi: 10.3390/genes15040450.
Transcription factors (TFs) are proteins essential for the regulation of gene expression, and they regulate the genes involved in different cellular processes, such as proliferation, differentiation, survival, and apoptosis. Although their expression is essential in normal physiological conditions, abnormal regulation of TFs plays critical role in several diseases, including cancer. In prostate cancer, the most common malignancy in men, TFs are known to play crucial roles in the initiation, progression, and resistance to therapy of the disease. Understanding the interplay between these TFs and their downstream targets provides insights into the molecular basis of prostate cancer pathogenesis. In this review, we discuss the involvement of key TFs, including the E26 Transformation-Specific (ETS) Family (ERG and SPDEF), NF-κB, Activating Protein-1 (AP-1), MYC, and androgen receptor (AR), in prostate cancer while focusing on the molecular mechanisms involved in prostate cancer development. We also discuss emerging diagnostic strategies, early detection, and risk stratification using TFs. Furthermore, we explore the development of therapeutic interventions targeting TF pathways, including the use of small molecule inhibitors, gene therapies, and immunotherapies, aimed at disrupting oncogenic TF signaling and improving patient outcomes. Understanding the complex regulation of TFs in prostate cancer provides valuable insights into disease biology, which ultimately may lead to advancing precision approaches for patients.
转录因子（TFs）是调节基因表达所必需的蛋白质，它们调节参与不同细胞过程的基因，如增殖、分化、存活和凋亡。尽管它们的表达在正常生理条件下至关重要，但TFs的异常调节在包括癌症在内的多种疾病中起着关键作用。在前列腺癌（男性中最常见的恶性肿瘤）中，已知TFs在该疾病的起始、进展和治疗抵抗中发挥关键作用。了解这些TFs与其下游靶点之间的相互作用，有助于深入了解前列腺癌发病机制的分子基础。在本综述中，我们讨论了关键TFs的参与情况，包括E26转化特异性（ETS）家族（ERG和SPDEF）、核因子κB（NF-κB）、活化蛋白-1（AP-1）、MYC和雄激素受体（AR）在前列腺癌中的作用，同时关注前列腺癌发展所涉及的分子机制。我们还讨论了使用TFs的新兴诊断策略、早期检测和风险分层。此外，我们探讨了针对TF途径的治疗干预措施的发展，包括使用小分子抑制剂、基因疗法和免疫疗法，旨在破坏致癌TF信号并改善患者预后。了解前列腺癌中TFs的复杂调节，为疾病生物学提供了有价值的见解，最终可能会推动针对患者的精准治疗方法的发展。
