Table 2 Oncogenic/tumor-suppressive role of DDX3X in various cancers

Glioma

Oncogenic

Protein expression; Positively correlated with Snail

-

[77]

-

[78]

Medulloblastoma (MB)

Oncogenic

Protein expression

-

[79]

Mutations

Mutations led to alteration of protein function

[80–82]

Inhibitor therapy

Inhibiting WNT/β-catenin signaling

[79]

Meningioma

Oncogenic

Protein expression

-

[83]

Unknown

Mutations

-

[84]

Head and neck squamous cell carcinoma (HNSSC)

Oncogenic

Protein expression

-

[29, 85]

Tumor-suppressive

Protein expression

-

[49]

Stemness

-

[86]

Promoting metastasis

Cooperating with CBC complex and eIF3 to promote ATF4 translation

[29]

Inhibitor therapy

-

[86, 87]

Cutaneous squamous cell carcinoma (cSCC)

Tumor-suppressive

Protein expression

-

[20]

Melanoma

Oncogenic

Stemness

-

[88]

Tumor-suppressive

Mutations

Mutations mostly led to loss of function

[30]

Repressing metastasis

Promoting MITF translation

[30]

Lung cancer

Oncogenic

Protein expression

-

[89]

Stemness

-

[91]

Inhibitor therapy

Inhibiting Wnt/β-catenin pathway activity; impairing radiation-induced DNA double-strand break (DSB)

[90]

Tumor-suppressive

Protein expression

-

[26, 92]

Repressing proliferation

Synergistically enhancing P53-activated P21 transcription

[92]

Repressing metastasis

Promoting MDM2 transcription to prevent E-cadherin degradation

[26]

Mesothelioma

Unknown

Mutations

-

[93, 94]

Breast cancer

Oncogenic

Protein expression

-

[95]

Inducing tumorigenesis

-

[24]

Hypoxia responsive

Directly regulated by HIF-1α

[96]

Promoting proliferation

Downregulating KLF4 expression via altering KLF4 mRNA exon usage; downregulating P21

[24, 97]

Promoting metastasis

upregulating E-cadherin expression via interacting to its promoter

[24]

Inhibitor therapy

Targeting mitochondria translation

[50]

Hepatocellular carcinoma (HCC)

Oncogenic

Protein expression

-

[90]

Inducing tumorigenesis

-

[90]

Tumor-suppressive

Protein expression

-

[20, 23]

Reducing tumorigenesis

Maintaining genome stability

[12]

Repressing stemness

Upregulating the expression of a subset of tumor-suppressive miRNAs via reducing DNMT3A activity

[66]

Repressing global protein synthesis

Interacting with eIF4E and inhibiting its activity

[18]

Gallbladder carcinoma

Oncogenic

Protein expression

-

[28]

Pancreatic ductal adenocarcinoma (PDAC)

Oncogenic

Protein expression

-

[27]

Colorectal carcinoma (CRC)

Oncogenic

Protein expression

-

[98, 99]

Promoting metastasis

DDX3X/KRAS/ERK/AKT/β-catenin/ZEB1 axis; DDX3X/CK1ε/Dvl2 axis; DDX3X/KRAS/HIF-1α/YAP1/SIX2 axis

[100–102]

Drug resistance

DDX3X/YAP1/SIX2 axis

[102]

Inhibitor therapy

Inhibiting WNT/β-catenin signaling; mitochondrial swelling and increased ROS production

[98, 99]

Tumor-suppressive

Protein exprssion

-

[103]

Repressing metastasis

DDX3X/Snail/E-cadherin axis

[103]

Prostate cancer

Oncogenic

Protein expression

-

[104]

Inhibitor therapy

Radiosensitizing prostate cancer cell

[104]

Ewing sarcoma

Oncogenic

Protein expression

-

[105]

Inhibitor therapy

repressing translation of proteins with conserved biologic functions

[105]

Chronic lymphocytic leukemia (CLL)

Unknown

-

-

[106–108]

T-cell acute lymphoblastic leukemia (T-ALL)

Oncogenic

Fusion with MLLT10

-

[31, 109]

Natural killer/T-cell lymphoma (NKTCL)

Tumor-suppressive

Repressing proliferation

-

[42]

Mutations

Abnormal activated NF-κB and MAPK pathways

[42]

Aggressive natural killer-cell leukemia (ANKL)

Unknown

Mutations

-

[110]

Burkitt lymphoma (BL)

Unknown

Mutations

-

[161]

Burkitt-like lymphoma with 11q aberration (BLL-11q)

Unknown

Mutations

-

[111]

Various cell lines: Hela, Huh7, HCT116

Tumor-suppressive

Repressing proliferation

Promoting P21 transcription via interacting with SP1

[20]

Various cell lines: OVCAR3 ES2, A549 H1437, SUM159, HCC1500,

HT1080

Tumor-suppressive

Substrate of CMA

-

[162]

Various cell lines: MDA-MB-231, 1321N1, Jurkat, HeLa

Oncogenic

Anti-apoptosis

Cooperating with GSK3 and cIAP-1 to confront with extrinsic apoptosis signaling

[45]

P53 wide-type cell line: MCF-7, SH-SY5Y

Tumor-suppressive

Promoting DNA damage-induced apoptosis

Stabilizing P53 expression via interacting with it

[112]

P53 non-function or mutation cell line: Hela, MDA-MB-231

Oncogenic

Repressing DNA damage-induced apoptosis

-

[112]

Hela cell line

Tumor-suppressive

Promoting proper chromosome segregation

Interacting with hCAP-H

[35]

Various cell lines: HCT116, U2OS

Tumor-suppressive

Ensuring bipolar mitosis

Colocalizing with P53 in centrosome via upregulating P53 expression and phosphorylating P53 to inactivate and coalesce excess centrosome

[4]

Various cell lines: N2A, Hela

Oncogenic

Promoting metastasis

DDX3X/Rac1/β-catenin axis

[36]

Various cell lines: MKN-45, AGS

Oncogenic

Facilitating β-catenin signaling

Transactivating YY1 in the help of circ-CTNNB1

[51]

Hela cell line

Oncogenic

Promoting protein synthesis

Interacting with eIF3

[17]

Anti-apoptosis

Downregulating P21 expression

[113]

Various cell lines: Hela, H1299, A549 and U2OS

Oncogenic

Promoting G1/S phase transition

Promoting cyclin E1 translation

[33]