DDX3X and Stress Granules: Emerging Players in Cancer and Drug Resistance

Simple Summary The prevalence of drug resistance has become a global concern, impacting the effectiveness of various cancer treatments. One of the mechanisms of drug resistance involves cellular stress response, in which stress granules (SGs) form against pharmacological stress. Recent research pointed out that an SGs component, DEAD-box helicase 3 X-linked (DDX3X) protein, is upregulated in multiple cancers, but its role in cancer drug resistance has yet to be fully understood. This review aims to describe the relationship among DDX3X, SGs, and drug resistance in depth.Abstract 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.