Taniguchi, Hiroaki

写真a

Affiliation

School of Medicine, Clinical and Translational Research Center (Shinanomachi)

Position

Project Associate Professor (Non-tenured)

 

Papers 【 Display / hide

  • The evolving landscape of cancer stem cells and ways to overcome cancer heterogeneity

    Taniguchi H., Suzuki Y., Natori Y.

    Cancers (Cancers)  11 ( 4 )  2019.04

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    © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Cancer stem cells (CSCs) with therapeutic resistance and plasticity can be found in various types of tumors and are recognized as attractive targets for treatments. As CSCs are derived from tissue stem or progenitor cells, and/or dedifferentiated mature cells, their signal transduction pathways are critical in the regulation of CSCs; chronic inflammation causes the accumulation of genetic mutations and aberrant epigenetic changes in these cells, potentially leading to the production of CSCs. However, the nature of CSCs appears to be stronger than the treatments of the past. To improve the treatments targeting CSCs, it is important to inhibit several molecules on the signaling cascades in CSCs simultaneously, and to overcome cancer heterogeneity caused by the plasticity. To select suitable target molecules for CSCs, we have to explore the landscape of CSCs from the perspective of cancer stemness and signaling systems, based on the curated databases of cancer-related genes. We have been studying the integration of a broad range of knowledge and experiences from cancer biology, and also from other interdisciplinary basic sciences. In this review, we have introduced the concept of developing novel strategies targeting CSCs.

  • Silencing PRDM14 via oligonucleotide therapeutics suppresses tumorigenicity and metastasis of breast cancer

    Taniguchi H., Imai K.

    Methods in Molecular Biology (Methods in Molecular Biology)  1974   233 - 243 2019

    ISSN  10643745

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    © Springer Science+Business Media, LLC, part of Springer Nature 2019. The PRDI-BF1 and RIZ (PR) domain zinc finger protein 14 (PRDM14) is upregulated in approximately 60% of breast cancers, some of which exhibit gene amplification. In contrast, PRDM14 is not expressed in normal, and differentiated tissues. PRDM14+ breast cancer cells are resistant to chemotherapy drugs, are tumorigenic, and metastasize to the lungs. It is commonly assumed that genes that are overexpressed in cancers, such as PRDM14, are effective targets for new therapies that specifically abrogate the expression of these genes. RNA interference of PRDM14, a gene expressed by breast cancer cells, reduced the size of tumors and lung metastases in nude mice. In this chapter, we introduce the concept and methods to develop and apply systematically injected small interfering RNA therapy for breast cancer models in vivo.

  • PRDM14 is overexpressed in chronic pancreatitis prior to pancreatic cancer

    Moriya C., Imai K., Taniguchi H.

    FEBS Open Bio (FEBS Open Bio)  8 ( 10 ) 1733 - 1741 2018.10

    ISSN  22115463

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    © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer that is typically diagnosed at a later stage with metastases and is difficult to treat. Therefore, investigating the mechanism of PDAC initiation is important to aid early-stage cancer detection. PRDM14 is a transcription factor that maintains pluripotency in embryonic stem cells and is overexpressed in several cancers. We previously reported that PRDM14 is overexpressed and regulates cancer stem-like phenotypes in PDAC, and herein, we assess whether PRDM14 expression increases prior to tumorigenesis. Through immunohistochemistry analyses of clinical tissues, we detected PRDM14-positive cells in precursor pancreatic intraepithelial neoplasia and chronic pancreatitis, which is a risk factor for PDAC, lesions. PRDM14 staining in chronic pancreatitis was as high as that in PDAC and cancer adjacent tissues. We induced pancreatitis in mouse models by cerulein injection, and observed that PRDM14 expression increased in chronic pancreatitis models but not in control or acute pancreatitis mice. Moreover, cerulein treatment increased PRDM14 expression in PK-1 and AsPC-1 pancreatic cancer cell lines. Our results suggest that inflammation increases the expression of PRDM14, which regulates cancer stem-like phenotypes, and this occurs prior to PDAC initiation and progression.

  • PRDM14 directly interacts with heat shock proteins HSP90α and glucose-regulated protein 78

    Moriya C., Taniguchi H., Nagatoishi S., Igarashi H., Tsumoto K., Imai K.

    Cancer Science (Cancer Science)  109 ( 2 ) 373 - 383 2018.02

    ISSN  13479032

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    © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 need to be clarified. Here, we identified the proteins interacting with PRDM14 in triple-negative breast cancer (TNBC) cells, which do not express the three most common types of receptor (estrogen receptors, progesterone receptors, and HER2). We obtained 13 candidates that were pulled down with PRDM14 in TNBC HCC1937 cells and identified them by mass spectrometry. Two candidates—glucose-regulated protein 78 (GRP78) and heat shock protein 90-α (HSP90α)—were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance analysis using GST-PRDM14 showed that these two proteins directly interacted with PRDM14 and that the interactions required the C-terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem-like CD24− CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggest that HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.

  • PRDM14, a zinc finger protein, regulates cancer stemness

    Taniguchi H., Imai K.

    Methods in Molecular Biology (Methods in Molecular Biology)  1867   3 - 13 2018

    ISSN  10643745

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    © 2018, Springer Science+Business Media, LLC, part of Springer Nature. PRDI-BF1 and RIZ homology (PR) domain zinc finger protein 14 (PRDM14) contains a PR domain related to the SET methyltransferase domain and zinc finger motifs. PRDM14 maintains stemness in embryonic stem cells and primordial germ cells via epigenetic mechanisms. PRDM14, however, is not expressed in normal differentiated tissues. We and other groups previously reported that PRDM14 expression is markedly higher in some types of cancers compared to the corresponding normal tissues. PRDM14 confers stem cell-like characteristics upon cancer cells, such as sphere formation, dye efflux, chemotherapy resistance, proliferation, and distant metastasis. Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the primary causes of cancer-related deaths. Because CSCs are also thought to be resistant to conventional therapies, an effective and novel therapeutic approach for CSCs is imperative. RNAi silencing of PRDM14 expressed by breast and pancreatic cancer cells reduced tumor size and distant metastasis of these cells in nude mice. Inhibition of PRDM14 expression by cancer cells may be an effective and radical therapy for solid cancers. In this chapter, we discuss methods for studying CSC-like properties in cancer cells and describe the use of siRNA with a drug delivery system by systemic injection in vivo.