title: Multifunctional DDX3: dual roles in various cancer development and its related signaling pathways.
abstract: DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box protein, which is a cluster of ATP-dependent and the largest family of RNA helicase. DEAD-box family is characterized by the regulation of ATPase and helicase activities, the modulation of RNA metabolism, and the actors of RNA binding proteins or molecular chaperones to interact with other proteins or RNA. For DDX3, it exerts its multifaceted roles in viral manipulation, stress response, hypoxia, radiation response and apoptosis, and is closely related to cancer development and progression. DDX3 has dual roles in different cancer types and can act as either an oncogene or tumor suppressor gene during cancer progression. In the present review, we mainly provide an overview of current knowledge on dual roles of DDX3 in various types of cancer, including breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, oral squamous cell carcinoma, Ewing sarcoma, glioblastoma multiforme and gallbladder carcinoma, and illustrate the regulatory mechanisms for leading these two controversial biological effects. Furthermore, we summarize the essential signaling pathways that DDX3 participated, especially the Wnt/β-catenin signaling and EMT related signaling (TGF-β, Notch, Hedgehog pathways), which are crucial to DDX3 mediated cancer metastasis process. Thoroughly exploring the dual roles of DDX3 in cancer development and the essential signaling pathways it involved, it will help us open new perspectives to develop novel promising targets to elevate therapeutic effects and facilitate the "Personalized medicine" or "Precision medicine" to come into clinic.
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South UniversityChangsha 410008, Hunan, China; Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South UniversityChangsha 410013, Hunan, China; Department of Dermatology, Xiangya Hospital, Central South UniversityChangsha 410008, Hunan, China.
authors.forename: Luqing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South UniversityChangsha 410008, Hunan, China; Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South UniversityChangsha 410013, Hunan, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Computer Science and Engineering, South China University of Technology Guangzhou 510640, Guangdong, China.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, School of Basic Medical Science, Xiangya School of Medicine, Central South University Changsha 410013, Hunan, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
keywords: DDX3; EMT related pathway; Wnt/β-catenin pathway; cancer; oncogene; tumor suppressor gene