Table 1.

Dual roles of DDX3 in cancer development

Cancer type	Roles	Possible pathways and mechanisms	DDX3 inhibitors	Refs
Breast cancer	Oncogene	“HIF-1α-DDX3-E-cadherin-EMT” pathway, promote metastasis	NZ51 (a ring-expanded nucleoside analogue (REN), incorporate into the ATP binding pocket of DDX3)	[20-23]
Lung cancer	Oncogene/TSG	Oncogene: “DDX3-Wnt/β-catenin” pathway, affect apoptosis process	RK-33 (a small molecule inhibitor, bind to the ATP-binding site of DDX3)	[25-27]
		TSG: “p53-DDX3-p21” pathway, affect apoptosis process
		“p53-DDX3-MDM2-Slug-E-cadherin” pathway, suppress EMT and metastasis
Colorectal cancer	Oncogene/TSG	Oncogene: “DDX3-Wnt/β-catenin-TCF4” pathway, affect cell cycle progression	RK-33 (a small molecule inhibitor, bind to the ATP-binding site of DDX3)	[28,29]
		TSG: DDX3 inhibits Snail expression, and prevents EMT
Hepatocellular carcinoma (HCC)	TSG	DDX3 down-regulates cyclinD1, and up-regulates p21, impede cell cycle progression	None	[35,36]
		“DDX3-Sp1-p21” pathway, affect apoptosis process
Oral squamous cell carcinoma (OSCC)	Oncogene/TSG	Oncogene: promote OSCC progression	Ketorolac salt (bioactive compound, inhibit the ATP hydrolysis process of DDX3)	[37,38]
		TSG: DDX3 is a protective factor and a good survival predictor
Ewing sarcoma	Oncogene	Promote Ewing sarcoma progression and the resistance to chemotherapy	RK-33 (a small molecule inhibitor, bind to the ATP-binding site of DDX3)	[39]
Glioblastoma multiforme (GBM)	Oncogene	Impede the death receptor mediated apoptosis process, elevate Snail expression, and promote metastasis	To be developed	[44]
Gallbladder carcinoma	Oncogene	High DDX3 level is correlated with large tumor size, high TNM stage, lymph node metastasis, and poor prognosis	To be developed	[45]

Abbreviations: TSG: Tumor Suppressor Gene; EMT: Epithelial-Mesenchymal Transition; TCF: T-Cell Factor; TNM: Tumor, Node, Metastasis.