Zhang Han, Mañán-Mejías Paula M, Miles Hannah N, Putnam Andrea A, MacGillivray Leonard R, Ricke William A
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Cancers (Basel). 2024 Mar 12;16(6):1131. doi: 10.3390/cancers16061131.
The DEAD (Asp-Glu-Ala-Asp)-box helicase 3 X-linked (DDX3X) protein participates in many aspects of mRNA metabolism and stress granule (SG) formation. DDX3X has also been associated with signal transduction and cell cycle regulation that are important in maintaining cellular homeostasis. Malfunctions of DDX3X have been implicated in multiple cancers, including brain cancer, leukemia, prostate cancer, and head and neck cancer. Recently, literature has reported SG-associated cancer drug resistance, which correlates with a negative disease prognosis. Based on the connections between DDX3X, SG formation, and cancer pathology, targeting DDX3X may be a promising direction for cancer therapeutics development. In this review, we describe the biological functions of DDX3X in terms of mRNA metabolism, signal transduction, and cell cycle regulation. Furthermore, we summarize the contributions of DDX3X in SG formation and cellular stress adaptation. Finally, we discuss the relationships of DDX3X, SG, and cancer drug resistance, and discuss the current research progress of several DDX3X inhibitors for cancer treatment.
DEAD（天冬氨酸-谷氨酸-丙氨酸-天冬氨酸）盒解旋酶3 X连锁（DDX3X）蛋白参与mRNA代谢和应激颗粒（SG）形成的多个方面。DDX3X还与信号转导和细胞周期调控相关，这些对于维持细胞稳态很重要。DDX3X功能异常与多种癌症有关，包括脑癌、白血病、前列腺癌和头颈癌。最近，文献报道了与SG相关的癌症耐药性，这与不良的疾病预后相关。基于DDX3X、SG形成和癌症病理之间的联系，靶向DDX3X可能是癌症治疗药物开发的一个有前景的方向。在这篇综述中，我们从mRNA代谢、信号转导和细胞周期调控方面描述了DDX3X的生物学功能。此外，我们总结了DDX3X在SG形成和细胞应激适应中的作用。最后，我们讨论了DDX3X、SG和癌症耐药性的关系，并讨论了几种用于癌症治疗的DDX3X抑制剂的当前研究进展。
