Li Xiaomeng, Rasul Azhar, Sharif Farzana, Hassan Mudassir
KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Zoology, Government College University Faisalabad, Faisalabad, Pakistan.
Front Oncol. 2024 Mar 25;14:1376633. doi: 10.3389/fonc.2024.1376633. eCollection 2024.
Protein inhibitors of activated STATs (PIAS) are proteins for cytokine signaling that activate activator-mediated gene transcription. These proteins, as versatile cellular regulators, have been described as regulators of approximately 60 proteins. Dysregulation of PIAS is associated with inappropriate gene expression that promotes oncogenic signaling in multiple cancers. Multiple lines of evidence have revealed that PIAS family members show modulated expressions in cancer cells. Most frequently reported PIAS family members in cancer development are PIAS1 and PIAS3. SUMOylation as post-translational modifier regulates several cellular machineries. PIAS proteins as SUMO E3 ligase factor promotes SUMOylation of transcription factors tangled cancer cells for survival, proliferation, and differentiation. Attenuated PIAS-mediated SUMOylation mechanism is involved in tumorigenesis. This review article provides the PIAS/SUMO role in the modulation of transcriptional factor control, provides brief update on their antagonistic function in different cancer types with particular focus on PIAS proteins as a bonafide therapeutic target to inhibit STAT pathway in cancers, and summarizes natural activators that may have the ability to cure cancer.
信号转导和转录激活因子（STAT）激活蛋白抑制剂（PIAS）是细胞因子信号传导蛋白，可激活激活剂介导的基因转录。这些蛋白质作为多功能细胞调节剂，已被描述为约60种蛋白质的调节剂。PIAS失调与不适当的基因表达相关，后者在多种癌症中促进致癌信号传导。多条证据表明，PIAS家族成员在癌细胞中表现出表达调节。在癌症发展中最常报道的PIAS家族成员是PIAS1和PIAS3。SUMO化作为翻译后修饰调节多种细胞机制。PIAS蛋白作为SUMO E3连接酶因子促进转录因子的SUMO化，使癌细胞纠结以实现存活、增殖和分化。PIAS介导的SUMO化机制减弱与肿瘤发生有关。这篇综述文章阐述了PIAS/SUMO在调节转录因子控制中的作用，简要介绍了它们在不同癌症类型中的拮抗功能，特别关注PIAS蛋白作为抑制癌症中STAT途径的真正治疗靶点，并总结了可能具有治愈癌症能力的天然激活剂。
