DEAD/H (Asp–Glu–Ala–Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells

Koshio, Jun; Kagamu, Hiroshi; Nozaki, Kohei; Saida, Yu; Tanaka, Tomohiro; Shoji, Shuichi; Igarashi, Natsue; Miura, Satoru; Okajima, Masaaki; Watanabe, Satoshi; Yoshizawa, Hirohisa; Narita, Ichiei

doi:10.1007/s00262-013-1467-x

Cited by 26 publications

(26 citation statements)

References 29 publications

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“…Understanding the role of nuclear DDX3 expression in tumors is relevant given DDX3’s function in RNA processing and its known nucleocytoplasmic shuttling capacities. DDX3 has been found to promote oncogenesis and DDX3 inhibitors are being developed for colorectal13 and breast cancers17 among other malignancies 12,18,33,34. In addition, DDX3 is essential for the nuclear export of the human immunodeficiency virus 1 (HIV-1) protein Rev and is, therefore, also a potential therapeutic target in the treatment of HIV infections 35,36.…”

Section: Discussionmentioning

confidence: 99%

Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer

Voss¹,

Vesuna²,

Bol³

et al. 2017

OTT

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PurposeDEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer.MethodsExpression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples. Correlations between the subcellular localization of DDX3 and CRM1 and the difference in overall survival between patients with and without nuclear DDX3 were studied. In addition, DDX3 mutants were created for in vitro evaluation of the mechanism behind nuclear retention of DDX3.ResultsDDX3 was present in the nucleus of 35% of colorectal and 48% of breast cancer patient samples and was particularly strong in the nucleolus. Nuclear DDX3 correlated with worse overall survival in both colorectal (hazard ratio [HR] 2.34, P<0.001) and breast cancer (HR 2.39, P=0.004) patients. Colorectal cancers with nuclear DDX3 expression more often had cytoplasmic expression of the nuclear exporter CRM1 (relative risk 1.67, P=0.04). In vitro analysis of DDX3 deletion mutants demonstrated that CRM1-mediated export was most dependent on the N-terminal nuclear export signal.ConclusionOverall, we conclude that nuclear DDX3 is partially CRM1-mediated and predicts worse survival in colorectal and breast cancer patients, putting it forward as a target for therapeutic intervention with DDX3 inhibitors under development in these cancer types.

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Section: Discussionmentioning

confidence: 99%

Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer

Voss¹,

Vesuna²,

Bol³

et al. 2017

OTT

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“…Vaccination with synthesized DDX3X protein exhibited therapeutic efficacy against established skin melanoma, effecting curing of the tumor. Because DDX3X is expressed in breast cancer cells, this finding indicates that anti-DDX3X immunotherapy may be a promising strategy (Koshio et al 2013). Tumor growth was lower when paclitaxel was delivered through polymeric nanoparticles targeting CD133 (Swaminathan et al 2013).…”

Section: Cd133 As a Biomarker In Chemoradiotherapeutic Response In Brmentioning

confidence: 97%

CD133 as Biomarker in Breast Cancer

Matsuoka

Yashiro

2014

Biomarkers in Cancer

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Breast cancer is one of the most common malignant diseases worldwide. Prognosis of breast cancer is still poor despite the diagnostic and therapeutic progress in recent years. In order to decrease breast cancerrelated deaths, many studies are aimed at identifying novel screening-and prognosis-related biomarkers. Cancer stem cells (CSCs) are characterized by the capacity for self-renewal, tumorigenesis, and differentiation. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of CSC markers have been of great interest. CD133, five transmembrane single-chain glycoproteins, has been successfully used as a stem cell marker to identify and isolate CSCs in malignant tumors. CD133 can also be used to predict tumor metastasis, patient survival and resistance to therapy. This chapter provides an overview of the evidence regarding the existence and function of CD133 in breast cancers in the context of the experimental and clinical data. It also discusses CD133 as a possible target for breast cancer therapy.

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“…1 and Table 1) [64,65]. On the other hand, CD133 + CSCs/CICs isolated from melanoma were shown to express either NY-ESO-1 or DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) representing target of tumor-specific T cells [90,91]. Other studies have described the isolation of T lymphocytes recognizing TAAs expressed by CSCs/CICs such as IL-13Rα2, SOX2 and CD133 in GBM, CEP55 and COA-1 in CRC and EpCAM in retinoblastoma (Table 1) [28,65,71,92].…”

Section: Tumor Associated Antigens and Adaptive Immune Responses Agaimentioning

confidence: 99%

The Cross Talk between Cancer Stem Cells/Cancer Initiating Cells and Tumor Microenvironment: The Missing Piece of the Puzzle for the Efficient Targeting of these Cells with Immunotherapy

Ravindran

Rasool

Maccalli

2019

Cancer Microenvironment

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Cancer Stem Cells/Cancer Initiating Cells (CSCs/CICs) is a rare sub-population within a tumor that is responsible for tumor formation, progression and resistance to therapies. The interaction between CSCs/CICs and tumor microenvironment (TME) can sustain "stemness" properties and promote their survival and plasticity. This cross-talk is also pivotal in regulating and modulating CSC/CIC properties. This review will provide an overview of the mechanisms underlying the mutual interaction between CSCs/CICs and TME. Particular focus will be dedicated to the immunological profile of CSCs/CICs and its role in orchestrating cancer immunosurveillance. Moreover, the available immunotherapy strategies that can target CSCs/CICs and of their possible implementation will be discussed. Overall, the dissection of the mechanisms regulating the CSC/CIC-TME interaction is warranted to understand the plasticity and immunoregulatory properties of stem-like tumor cells and to achieve complete eradications of tumors through the optimization of immunotherapy.

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DEAD/H (Asp–Glu–Ala–Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells

Cited by 26 publications

References 29 publications

Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer

Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer

CD133 as Biomarker in Breast Cancer

The Cross Talk between Cancer Stem Cells/Cancer Initiating Cells and Tumor Microenvironment: The Missing Piece of the Puzzle for the Efficient Targeting of these Cells with Immunotherapy

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