DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer

Su, Chih-Chung; Lin, Tsung-Chieh; Lin, Yuan; Chen, Ming-Huang; Lee, Chien Hsin; Wang, Hsuan Yao; Lee, Yu-Cheng; Liu, Yu Peng; Chen, Chi Long; Hsiao, Michael

doi:10.18632/oncotarget.4329

Cited by 47 publications

(34 citation statements)

References 32 publications

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“…Although there are some controversial data indicating that DDX3 is a tumor suppressor (39–41), it is possible that the function of DDX3 is organ-specific. Our previous data in lung cancer indicate that inhibition of DDX3 function by a small-molecule inhibitor, RK-33, reduces cell proliferation in lung cancer and radiosensitizes lung cancer cells in a DDX3-dependent manner (19).…”

Section: Discussionmentioning

confidence: 99%

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

et al. 2016

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Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. RK-33 treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) decreased proliferation and induced a G1 phase cell-cycle arrest. Conversely, the low DDX3–expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a radiosensitizer. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer.

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Section: Discussionmentioning

confidence: 99%

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

et al. 2016

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“…Several studies showed that DDX3 acts as a tumor suppressor in colorectal cancer. Knockdown of DDX3 increases cancer progression through Snail/E-cadherin pathway in colon cancer cells (36). In addition, colorectal cancer patients with low DDX3 expression have poor prognosis and more frequent distant metastasis (36).…”

Section: Ddx3 Role In Cancer: Tumor Suppressor or Oncogenementioning

confidence: 99%

“…DDX3 knockdown downregulates Snail levels and decreases cell proliferation and migration in breast cancer MCF-7 cells (47). However, the inhibition of DDX3 induces the EMT process, with upregulation of Snail and decrease of E-cadherin in colorectal cancer DLD-1 and HCT116 cells (36).…”

Section: Multifunctions Of Ddx3-mediated Signaling Pathwaysmentioning

confidence: 99%

A double-edged function of DDX3, as an oncogene or tumor suppressor, in cancer progression (Review)

Zhang

Yang

et al. 2018

Oncol Rep

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DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box proteins in all eukaryotes from yeasts to human beings. Accumulating studies have confirmed DDX3 has the ability to regulate different steps of RNA metabolism, including RNA splicing, RNA export, transcription and translation initiation. Moreover, DDX3 is involved in many biological processes, such as stress response, cell apoptosis, cell cycle regulation and virus infection. In recent years, DDX3 is getting increasing attention due to its essential roles in cancer progression. However, DDX3 role in cancer development is rather complicated. This review mainly focuses on the dual roles of DDX3 and DDX3-mediated signaling pathways in multiple cancers. In addition, the interplaying causes for the controversial roles of DDX3 in cancer are discussed. So far several small molecular chemical compounds targeting DDX3 are also summarized from the anticancer activity to the clinical trials of DDX3 inhibitors.

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“…For instance, most of the recent studies demonstrated that DEAD-box RNA helicase 3 (DDX3) acts as an oncogenic role in breast cancer (Bol et al, 2013) , but some studies (Su et al, 2015) ( Zhao et al, 2016) also showed that its downregulation promotes metastasis in colorectal cancer indicating a potential role as TSG.…”

Section: Introductionmentioning

confidence: 99%

Moonlight: a tool for biological interpretation and driver genes discovery

Colaprico

Olsen²,

Cava

et al. 2018

Preprint

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Cancer is a complex and heterogeneous disease. It is crucial to identify the key driver genes and their role in cancer mechanisms with attention to different cancer stages, types or subtypes. Cancer driver genes are elusive and their discovery is complicated by the fact that the same gene can play a diverse role in different contexts. Key biological processes, such as cell proliferation and cell death, have been linked to cancer progression. Thus, in principle, they can be exploited to classify the cancer genes and unveil their role. Here, we present a new method, Moonlight, that exploit expression data to classify cancer genes. Moonlight relies on the integration of functional enrichment analysis, gene regulatory networks and upstream regulator analysis from expression data to score the importance of biological cancer-related processes taking into account either the inter-or intra-tumor heterogeneity. We then employed these scores to predict if each gene acts as a tumor suppressor gene (TSG) or as an oncogene (OCG). Our methodology also allow to predict genes with dual role, i.e. the moonlight genes (TSG in one cancer type or stage and OCG in another), as well as to elucidate the underlying biological processes.Availability: https://bioconductor.org/packages/MoonlightR & https://github.com/ibsquare/MoonlightR/

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DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer

Cited by 47 publications

References 32 publications

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3

A double-edged function of DDX3, as an oncogene or tumor suppressor, in cancer progression (Review)

Moonlight: a tool for biological interpretation and driver genes discovery

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