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连锁蛋白（DDX3X）参与mRNA代谢和应激颗粒形成的多个环节。该蛋白在信号传导和细胞周期调控中亦发挥重要作用，对维持细胞稳态至关重要。DDX3X功能异常与多种癌症的发生发展相关，包括脑癌、白血病、前列腺癌及头颈癌。近期研究报道应激颗粒介导的癌症耐药现象与不良疾病预后密切相关。基于DDX3X、应激颗粒形成与癌症病理之间的内在联系，靶向DDX3X可能成为癌症治疗研发的新方向。本文系统综述了DDX3X在mRNA代谢、信号传导和细胞周期调控中的生物学功能，总结了该蛋白在应激颗粒形成及细胞应激适应中的作用机制，深入探讨了DDX3X、应激颗粒与癌症耐药之间的关联，并评述了当前靶向DDX3X的抗癌抑制剂研究进展。
DDX3X and Stress Granules: Emerging Players in Cancer and Drug Resistance
肿瘤(癌症)患者之家