2026/03/11 更新

写真a

カイ　マサヒロ
甲斐　正広
所属
医学部 生化学講座分子生物学分野 講師
職名
講師
外部リンク

学位

  • 博士（理学）

研究キーワード

  • 生化学

研究分野

  • ライフサイエンス / 分子生物学

学歴

  • 東京工業大学

    - 1993年

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    国名： 日本国

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  • 東京工業大学

    - 1993年

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所属学協会

論文

  • Pan-Cancer Analysis Reveals AEBP1-Collagen Co-Expression and Its Potential Role in CAF-Mediated Tumor Stiffness. 国際誌

    Shohei Sekiguchi, Akira Yorozu, Megumi Watanabe, Fumika Okazaki, Satoshi Ohwada, Eiichiro Yamamoto, Takeshi Niinuma, Hiroshi Kitajima, Kazuya Ishiguro, Mitsunobu Saito, Masahiro Kai, Masashi Idogawa, Kenichi Takano, Akihiro Miyazaki, Hiroshi Ohguro, Hiromu Suzuki

    International journal of molecular sciences   26 ( 23 )   2025年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment that promote cancer progression and immune evasion. Adipocyte enhancer-binding protein 1 gene (AEBP1), which encodes aortic carboxypeptidase-like protein (ACLP), has been implicated in tissue remodeling and fibrosis, yet its role in CAF biology across cancers remains poorly understood. Here, we performed a pan-cancer transcriptomic analysis using The Cancer Genome Atlas (TCGA) and found that AEBP1 expression strongly correlates with expression of collagen family genes in the majority of solid tumors. Integration of single-cell RNA-sequencing datasets from breast and pancreatic cancers revealed that AEBP1 is predominantly expressed in CAFs, where it is co-expressed with collagens and CAF marker genes. Functional experiments using three-dimensional (3D) spheroids composed of oral squamous cell carcinoma (OSCC)-derived CAFs showed that AEBP1 knockdown significantly reduced spheroid stiffness without altering their morphology or size, indicating that ACLP contributes to the mechanical properties of tumor tissues. Together with earlier findings linking AEBP1/ACLP to reduced CD8+ T-cell infiltration, our results suggest that stromal AEBP1/ACLP enhances both extracellular matrix stiffness and immune suppression and highlights AEBP1/ACLP as a potential therapeutic target through which to remodel the tumor microenvironment and improve anti-tumor immunity.

    DOI： 10.3390/ijms262311474

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  • DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells

    Ayano Yoshido, Kazuya Ishiguro, Hiroshi Kitajima, Takeshi Niinuma, Kohei Kumegawa, Masaki Maezawa, Tomohide Tsukahara, Mutsumi Toyota, Akira Yorozu, Hajime Sasaki, Eiichiro Yamamoto, Masahiro Kai, Masashi Idogawa, Toshihiko Torigoe, Hiroshi Nakase, Reo Maruyama, Hiromu Suzuki

    Clinical Epigenetics   17 ( 1 )   2025年11月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

    Abstract

    Background

    DOT1L, a histone H3 lysine 79 (H3K79) methyltransferase, is a potential therapeutic target in various malignancies. In the present study, we aimed to clarify the anti-tumor effect of DOT1L inhibition in breast cancer.

    Methods

    Estrogen receptor (ER)-positive/HER2-negative breast cancer cells (MCF7) and ER-negative/HER2-positive cells (SKBR3) were treated with a DOT1L inhibitor (SGC0946, EPZ-5676), after which colony formation assays, cell cycle assays, flow cytometry, gene expression microarray analysis, chromatin immunoprecipitation sequencing (ChIP-seq) and single-cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) were performed. Genetic ablation of STING was performed using the CRISPR/Cas9 system.

    Results

    Treatment with a DOT1L inhibitor suppressed proliferation and induced cell cycle arrest and apoptosis in both ER-positive/HER2-negative and ER-negative/HER2-positive cells. Transcriptome and epigenome analysis revealed that DOT1L inhibition activated transcription of a number of interferon (IFN)-related genes (IRGs) in breast cancer cells. We also found that DOT1L inhibition upregulated type I and type III IFNs as well as cell surface human leukocyte antigen (HLA) class I expression. Notably, DOT1L inhibition induced DNA damage and upregulated levels of cytoplasmic DNA in breast cancer cells. CRISPR/Cas9-mediated knockout of STING in breast cancer cells significantly suppressed the IFN signaling activated by DOT1L inhibition and attenuated the anti-tumor effect. Moreover, scATAC-seq analysis revealed that DOT1L inhibition suppressed expression of ERBB2 in HER2-positive breast cancer cells.

    Conclusion

    These findings suggest that the anti-breast cancer effect of DOT1L inhibition is mediated by multiple mechanisms, including activation of innate immune signaling.

    その他リンク： https://link.springer.com/article/10.1186/s13148-025-02017-5/fulltext.html

    DOI： 10.1186/s13148-025-02017-5

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  • Upregulation of LINC02154 promotes esophageal cancer progression by enhancing cell cycling and epithelial-mesenchymal transition. 国際誌

    Kotoha Shimote, Takeshi Niinuma, Hiroshi Kitajima, Kazuya Ishiguro, Eiichiro Yamamoto, Gota Sudo, Akira Yorozu, Mutsumi Toyota, Masahiro Kai, Masashi Idogawa, Hiromu Suzuki

    Non-coding RNA research   14   107 - 116   2025年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.

    DOI： 10.1016/j.ncrna.2025.06.001

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  • DOT1L inhibition reprograms innate immunity to potentiate immunomodulatory drug responses in multiple myeloma

    Kazuya Ishiguro, Hiroshi Kitajima, Takeshi Niinuma, Reo Maruyama, Tomohide Tsukahara, Yoshihiko Hirohashi, Akari Takaya, Kohei Kumegawa, Ayano Yoshido, Shohei Sekiguchi, Hajime Sasaki, Akira Yorozu, Mutsumi Toyota, Masahiro Kai, Toshihiko Torigoe, Hiroshi Nakase, Hiromu Suzuki

    Cancer Letters   631   217941 - 217941   2025年10月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

    DOI： 10.1016/j.canlet.2025.217941

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  • HOXA11-As Promotes Lymph Node Metastasis Through Regulation of IFNL and HMGB Family Genes in Pancreatic Cancer. 国際誌

    Hayato Nishiyama, Takeshi Niinuma, Hiroshi Kitajima, Kazuya Ishiguro, Eiichiro Yamamoto, Gota Sudo, Hajime Sasaki, Akira Yorozu, Hironori Aoki, Mutsumi Toyota, Masahiro Kai, Hiromu Suzuki

    International journal of molecular sciences   25 ( 23 )   2024年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Recent studies have shown that long noncoding RNAs (lncRNAs) play pivotal roles in the development and progression of cancer. In the present study, we aimed to identify lncRNAs associated with lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC). We analyzed data from The Cancer Genome Atlas (TCGA) database to screen for genes overexpressed in primary PDAC tumors with lymph node metastasis. Our screen revealed 740 genes potentially associated with lymph node metastasis, among which were multiple lncRNA genes located in the HOXA locus, including HOXA11-AS. Elevated expression of HOXA11-AS was associated with more advanced tumor stages and shorter overall survival in PDAC patients. HOXA11-AS knockdown suppressed proliferation and migration of PDAC cells. RNA-sequencing analysis revealed that HOXA11-AS knockdown upregulated interferon lambda (IFNL) family genes and downregulated high-mobility group box (HMGB) family genes in PDAC cells. Moreover, HMGB3 knockdown suppressed proliferation and migration by PDAC cells. These results suggest that HOXA11-AS contributes to PDAC progression, at least in part, through regulation of IFNL and HMGB family genes and that HOXA11 AS is a potential therapeutic target in PDAC.

    DOI： 10.3390/ijms252312920

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  • SMOC1の発現低下は大腸鋸歯状腺腫の進展と相関する(Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas)

    青木 敬則, 高澤 啓, 山本 英一郎, 新沼 猛, 山野 泰穂, 原田 拓, 北嶋 洋志, 甲斐 正広, 仲瀬 裕志, 菅井 有, 小山内 誠, 鈴木 拓, 鈴木 拓

    日本癌学会総会記事   83回   P - 2258   2024年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • 口腔扁平上皮癌においてAEBP1はがん線維芽細胞の物理的特性に影響を与える(AEBP1 affects physical properties of cancer associated fibroblasts in oral squamous cell carcinoma)

    関口 翔平, 萬 顕, 岡崎 史佳, 山本 英一郎, 新沼 猛, 高澤 啓, 北嶋 洋志, 甲斐 正広, 小山内 誠, 廣橋 良彦, 鳥越 俊彦, 小島 隆, 高野 賢一, 宮崎 晃亘, 鈴木 拓, 鈴木 拓

    日本癌学会総会記事   83回   P - 2078   2024年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • 非コードRNAの短いopen reading frameから翻訳される大腸がん関連マイクロプロテインの探索(Screening for colorectal cancer-associated microproteins translated from short open reading frames within noncoding RNAs)

    北嶋 洋志, 高澤 啓, 新沼 猛, 石黒 一也, 甲斐 正広, 仲瀬 裕志, 鈴木 拓, 鈴木 拓

    日本癌学会総会記事   83回   P - 1039   2024年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • 腫瘍間質のAEBP1発現は口腔扁平上皮がんの進展を促進する(Stromal expression of AEBP1 promotes progression of oral squamous cell carcinoma)

    関口 翔平, 岡崎 史佳, 萬 顕, 山本 英一郎, 新沼 猛, 高澤 啓, 畠中 柚衣, 北嶋 洋志, 甲斐 正広, 小山内 誠, 廣橋 良彦, 鳥越 俊彦, 小島 隆, 高野 賢一, 宮崎 晃亘, 鈴木 拓

    日本癌学会総会記事   82回   1427 - 1427   2023年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • SMOC1のダウンレギュレーションは大腸鋸歯状腺腫の進展と関連する(Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas)

    青木 敬則, 高澤 啓, 山本 英一郎, 新沼 猛, 山野 泰穂, 原田 拓, 久保 俊之, 北嶋 洋志, 甲斐 正広, 仲瀬 裕志, 菅井 有, 小山内 誠, 鈴木 拓

    日本癌学会総会記事   82回   485 - 485   2023年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • 早期大腸がん浸潤先進部の分子解析(Molecular analysis in the invasive front of early colorectal cancers)

    須藤 豪太, 山本 英一郎, 青木 敬則, 高澤 啓, 吉戸 文乃, 新沼 猛, 久保 俊之, 原田 拓, 萬 顕, 北嶋 洋志, 甲斐 正広, 小山内 誠, 仲瀬 裕志, 鈴木 拓

    日本癌学会総会記事   82回   274 - 274   2023年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers

    Ayano Yoshido, Gota Sudo, Akira Takasawa, Hironori Aoki, Hiroshi Kitajima, Eiichiro Yamamoto, Takeshi Niinuma, Taku Harada, Toshiyuki Kubo, Hajime Sasaki, Kazuya Ishiguro, Akira Yorozu, Masahiro Kai, Akio Katanuma, Hiro‐o Yamano, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

    Journal of Gastroenterology and Hepatology   38 ( 2 )   301 - 310   2022年11月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

    Abstract

    Background and Aim

    The tumor microenvironment plays an essential role in the development and progression of colorectal cancer (CRC). We recently reported that crosstalk between CRC cells and tumor‐associated macrophages (TAMs) via serum amyloid A1 (SAA1) promotes invasion by T1 CRCs. In the present study, we aimed to clarify the role of neutrophils in early CRCs.

    Methods

    Immunohistochemical analysis of CD66b, chemokine CXC motif ligand 8 (CXCL8 or interleukin‐8, IL‐8) and matrix metalloproteinase‐9 (MMP‐9) was performed using primary T1 CRCs (n = 49). The HL‐60 human promyelocytic leukemia cell line and THP‐1 human monocytic leukemia cell line were used to obtain neutrophil‐like and macrophage‐like cells, respectively. Boyden chamber assays were used to analyze cell migration and invasion, and quantitative RT‐PCR was used to analyze gene expression.

    Results

    Immunohistochemical analysis revealed accumulation of neutrophils at the SAA1‐positive invasive front of T1 CRCs. Experiments using HL‐60 cells suggested that treatment with SAA1 induced neutrophil migration and expression of CXCL8 and MMP‐9 in neutrophils and that neutrophils promote CRC cell migration and invasion. Immunohistochemistry confirmed accumulation of CXCL8‐ or MMP‐9‐positive neutrophils at the SAA1‐positive invasive front of T1 CRCs. Moreover, co‐culture experiments using CRC, THP‐1 and HL‐60 cells suggested that CRC cells activated by macrophages upregulate CXCL8 and MMP‐9 in neutrophils.

    Conclusions

    Our results suggest that interplay between macrophages and CRC cells leads to recruitment of neutrophils to the invasive front of T1 CRCs and that SAA1 secreted by CRC cells activate neutrophils to promote invasion.

    その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jgh.16055

    DOI： 10.1111/jgh.16055

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  • DLEU1はインターフェロン関連遺伝子の発現とヒストン修飾を制御し口腔扁平上皮癌の進行を促進する

    畠中 柚衣, 新沼 猛, 西山 廣陽, 北嶋 洋志, 山本 英一郎, 甲斐 正広, 萬 顕, 関口 翔平, 荻 和弘, 宮崎 晃亘, 鈴木 拓

    日本癌学会総会記事   80回   [J14 - 4]   2021年9月

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    記述言語：英語   出版者・発行元：(一社)日本癌学会  

    医中誌

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  • An Integrated Epigenome and Transcriptome Analysis to Clarify the Effect of Epigenetic Inhibitors on GIST

    TAKESHI NIINUMA, HIROSHI KITAJIMA, EIICHIRO YAMAMOTO, REO MARUYAMA, HIRONORI AOKI, TAKU HARADA, KAZUYA ISHIGURO, GOTA SUDO, MUTSUMI TOYOTA, AYANO YOSHIDO, MASAHIRO KAI, HIROSHI NAKASE, TAMOTSU SUGAI, HIROMU SUZUKI

    Anticancer Research   41 ( 6 )   2817 - 2828   2021年6月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：International Institute of Anticancer Research  

    DOI： 10.21873/anticanres.15062

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  • Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1. 査読 国際誌

    Nishiyama K, Maruyama R, Niinuma T, Kai M, Kitajima H, Toyota M, Hatanaka Y, Igarashi T, Kobayashi JI, Ogi K, Dehari H, Miyazaki A, Yorozu A, Yamamoto E, Idogawa M, Sasaki Y, Sugai T, Tokino T, Hiratsuka H, Suzuki H

    Cell death & disease   9 ( 8 )   826 - 826   2018年8月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/s41419-018-0893-2

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  • A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors. 査読 国際誌

    Isosaka M, Niinuma T, Nojima M, Kai M, Yamamoto E, Maruyama R, Nobuoka T, Nishida T, Kanda T, Taguchi T, Hasegawa T, Tokino T, Hirata K, Suzuki H, Shinomura Y

    PloS one   10 ( 7 )   e0133754   2015年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1371/journal.pone.0133754

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  • Genome-wide profiling of chromatin signatures reveals epigenetic regulation of MicroRNA genes in colorectal cancer. 国際誌

    Hiromu Suzuki, Shintaro Takatsuka, Hirofumi Akashi, Eiichiro Yamamoto, Masanori Nojima, Reo Maruyama, Masahiro Kai, Hiro-O Yamano, Yasushi Sasaki, Takashi Tokino, Yasuhisa Shinomura, Kohzoh Imai, Minoru Toyota

    Cancer research   71 ( 17 )   5646 - 58   2011年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Altered expression of microRNAs (miRNA) occurs commonly in human cancer, but the mechanisms are generally poorly understood. In this study, we examined the contribution of epigenetic mechanisms to miRNA dysregulation in colorectal cancer by carrying out high-resolution ChIP-seq. Specifically, we conducted genome-wide profiling of trimethylated histone H3 lysine 4 (H3K4me3), trimethylated histone H3 lysine 27 (H3K27me3), and dimethylated histone H3 lysine 79 (H3K79me2) in colorectal cancer cell lines. Combining miRNA expression profiles with chromatin signatures enabled us to predict the active promoters of 233 miRNAs encoded in 174 putative primary transcription units. By then comparing miRNA expression and histone modification before and after DNA demethylation, we identified 47 miRNAs encoded in 37 primary transcription units as potential targets of epigenetic silencing. The promoters of 22 transcription units were associated with CpG islands (CGI), all of which were hypermethylated in colorectal cancer cells. DNA demethylation led to increased H3K4me3 marking at silenced miRNA genes, whereas no restoration of H3K79me2 was detected in CGI-methylated miRNA genes. DNA demethylation also led to upregulation of H3K4me3 and H3K27me3 in a number of CGI-methylated miRNA genes. Among the miRNAs we found to be dysregulated, many of which are implicated in human cancer, miR-1-1 was methylated frequently in early and advanced colorectal cancer in which it may act as a tumor suppressor. Our findings offer insight into the association between chromatin signatures and miRNA dysregulation in cancer, and they also suggest that miRNA reexpression may contribute to the effects of epigenetic therapy.

    DOI： 10.1158/0008-5472.CAN-11-1076

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  • IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype. 査読 国際誌

    Suzuki H, Igarashi S, Nojima M, Maruyama R, Yamamoto E, Kai M, Akashi H, Watanabe Y, Yamamoto H, Sasaki Y, Itoh F, Imai K, Sugai T, Shen L, Issa JP, Shinomura Y, Tokino T, Toyota M

    Carcinogenesis   31 ( 3 )   342 - 9   2010年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1093/carcin/bgp179

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  • Diacylglycerol kinase α enhances protein kinase Cζ-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-κB 査読

    Kai, M, Yasuda, S, Imai, S, Toyota, M, Kanoh, H, Sakane, F

    FEBS Lett.   583 ( 19 )   3265 - 3268   2009年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.febslet.2009.09.017

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  • Diacylglycerol kinase η augments C-Raf activity and B-Raf/C-Raf heterodimerization 査読

    Yasuda, S, Kai, M, Imai, S, Takeishi, K. Taketomi, A, Toyota, M, Kanoh, H, Sakane, F

    J. Biol. Chem.   284 ( 43 )   29559 - 29570   2009年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1074/jbc.M109.043604

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  • Diacylglycerol kinase delta associates with receptor for activated C kinase 1, RACK1 査読

    Shin-ichi Imai, Satoshi Yasuda, Masahiro Kai, Hideo Kanoh, Fumio Sakane

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS   1791 ( 4 )   246 - 253   2009年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.bbalip.2009.01.024

    Web of Science

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  • Rab7 regulates maturation of melanosomal matrix protein gp100/Pmel17/Silv 査読

    Akinori Kawakami, Fumio Sakane, Shin-Ichi Imai, Satoshi Yasuda, Masahiro Kai, Hideo Kanoh, Hai-Ying Jin, Kuninori Hirosaki, Toshiharu Yamashita, David E. Fisher, Kowichi Jimbow

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   128 ( 1 )   143 - 150   2008年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1038/sj.jid.5700964

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  • Phorbol ester and hydrogen peroxide synergistically induce the interaction of diacylglycerol kinase γ with the Src homology 2 and C1 domains of β2-chimaerin. 査読

    Yasuda, S, Kai, M, Imai, S, Kanoh, H, Sakane, F

    Biochem. J.   409 ( 1 )   95 - 106   2008年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1042/BJ20070848

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  • Tyrosine phosphorylation of beta2-chimaerin by Src-family kinase negatively regulates its Rac-specific GAP activity. 査読 国際誌

    Masahiro Kai, Satoshi Yasuda, Shin-Ichi Imai, Hideo Kanoh, Fumio Sakane

    Biochimica et biophysica acta   1773 ( 9 )   1407 - 15   2007年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    beta2-Chimaerin, an intracellular receptor for the second messenger diacylglycerol and phorbol esters, is a GTPase-activating protein (GAP) specific for Rac. beta2-Chimaerin negatively controls many Rac-dependent pathophysiological events including tumor development. However, the regulatory mechanism of beta2-chimaerin remains largely unknown. Here we report that beta2-chimaerin is tyrosine-phosphorylated by Src-family kinases (SFKs) upon cell stimulation with epidermal growth factor (EGF). Mutational analysis identified Tyr-21 in the N-terminal regulatory region as a major phosphorylation site. Intriguingly, the addition of SFK inhibitor and the replacement of Tyr-21 with Phe (Y21F) markedly enhanced Rac-GAP activity of beta2-chimaerin in EGF-treated cells. Moreover, the Y21F mutant inhibited integrin-dependent cell spreading, in which Rac1 plays a critical role, more strongly than wild-type beta2-chimaerin. These results suggest Tyr-21 phosphorylation as a novel, SFK-dependent mechanism that negatively regulates beta2-chimaerin Rac-GAP activity.

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  • Tyrosine phosphorylation of beta 2-chimaerin by Src-family kinase negatively regulates its Rac-specific GAP activity 査読

    Masahiro Kai, Satoshi Yasuda, Shin-ichi Imai, Hideo Kanoh, Fumio Sakane

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   1773 ( 9 )   1407 - 1415   2007年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.bbamcr.2007.05.004

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  • Diacylglycerol kinases: why so many of them? 査読 国際誌

    Fumio Sakane, Shin-Ichi Imai, Masahiro Kai, Satoshi Yasuda, Hideo Kanoh

    Biochimica et biophysica acta   1771 ( 7 )   793 - 806   2007年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating DAG to yield PA. To date, ten mammalian DGK isozymes have been identified. In addition to the C1 domains (protein kinase C-like zinc finger structures) conserved commonly in all DGKs, these isoforms possess a variety of regulatory domains of known and/or predicted functions, such as a pair of EF-hand motifs, a pleckstrin homology domain, a sterile alpha motif domain and ankyrin repeats. Beyond our expectations, recent studies have revealed that DGK isozymes play pivotal roles in a wide variety of signal transduction pathways conducting development, neural and immune responses, cytoskeleton reorganization and carcinogenesis. Moreover, there has been rapidly growing evidence indicating that individual DGK isoforms exert their specific roles through interactions with unique partner proteins such as protein kinase Cs, Ras guanyl nucleotide-releasing protein, chimaerins and phosphatidylinositol-4-phosphate 5-kinase. Therefore, an emerging paradigm for DGK is that the individual DGK isoforms assembled in their own signaling complexes should carry out spatio-temporally segregated tasks for a wide range of biological processes via regulating local, but not global, concentrations of DAG and/or PA.

    PubMed

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  • Diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha- -induced apoptosis of human melanoma cells through NF-kappa B activation 査読

    Kenji Yanagisawa, Satoshi Yasuda, Masahiro Kai, Shin-ichi Imai, Keiko Yamada, Toshiharu Yamashita, Kowichi Jimbow, Hideo Kanoh, Fumio Sakane

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS   1771 ( 4 )   462 - 474   2007年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.bbalip.2006.12.008

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  • Diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation. 査読 国際誌

    Kenji Yanagisawa, Satoshi Yasuda, Masahiro Kai, Shin-ichi Imai, Keiko Yamada, Toshiharu Yamashita, Kowichi Jimbow, Hideo Kanoh, Fumio Sakane

    Biochimica et biophysica acta   1771 ( 4 )   462 - 74   2007年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    We investigated the implication of diacylglycerol kinase (DGK) alpha (type I isoform) in melanoma cells because we found that this DGK isoform was expressed in several human melanoma cell lines but not in noncancerous melanocytes. Intriguingly, the overexpression of wild-type (WT) DGKalpha, but not of its kinase-dead (KD) mutant, markedly suppressed tumor necrosis factor (TNF)-alpha-induced apoptosis of AKI human melanoma cells. In the reverse experiment, siRNA-mediated knockdown of DGKalpha significantly enhanced the apoptosis. The overexpression of other type I isoforms (DGKbeta and DGKgamma) had, on the other hand, no detectable effects on the apoptosis. These results indicate that DGKalpha specifically suppresses the TNF-alpha-induced apoptosis through its catalytic action. We found that the overexpression of DGKalpha-WT, but not of DGKalpha-KD, further enhanced the TNF-alpha-stimulated transcriptional activity of an anti-apoptotic factor, NF-kappaB. Conversely, DGKalpha-knockdown considerably inhibited the NF-kappaB activity. Moreover, an NF-kappaB inhibitor blunted the anti-apoptotic effect of DGKalpha overexpression. Together, these results strongly suggest that DGKalpha is a novel positive regulator of NF-kappaB, which suppresses TNF-alpha-induced melanoma cell apoptosis.

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  • Diacylglycerol kinase γ interacts with and activates β2-chimaerin, a Rac-specific GAP, in response to epidermal growth factor. 査読

    Yasuda, S, Kai, M, Imai, S, Kanoh, H, Sakane, F

    FEBS Lett.   581 ( 3 )   551 - 557   2007年2月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1016/j.febslet.2007.01.022

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  • Lipid phosphate phosphatases 1 and 3 are localized in distinct lipid rafts 査読

    Masahiro Kai, Fumio Sakane, Yan-Jun Jia, Shin-ichi Imai, Satoshi Yasuda, Hideo Kanoh

    JOURNAL OF BIOCHEMISTRY   140 ( 5 )   677 - 686   2006年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1093/jb/mvj195

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  • Nuclear transportation of diacylglycerol kinase gamma and its possible function in the nucleus. 査読 国際誌

    Takehiro Matsubara, Yasuhito Shirai, Kei Miyasaka, Takuya Murakami, Yasuto Yamaguchi, Takehiko Ueyama, Masahiro Kai, Fumio Sakane, Hideo Kanoh, Toshiaki Hashimoto, Shinji Kamada, Ushio Kikkawa, Naoaki Saito

    The Journal of biological chemistry   281 ( 10 )   6152 - 64   2006年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Diacylglycerol kinases (DGKs) convert diacylglycerol (DG) to phosphatidic acid, and both lipids are known to play important roles in lipid signal transduction. Thereby, DGKs are considered to be a one of the key players in lipid signaling, but its physiological function remains to be solved. In an effort to investigate one of nine subtypes, we found that DGKgamma came to be localized in the nucleus with time in all cell lines tested while seen only in the cytoplasm at the early stage of culture, indicating that DGKgamma is transported from the cytoplasm to the nucleus. The nuclear transportation of DGKgamma didn't necessarily need DGK activity, but its C1 domain was indispensable, suggesting that the C1 domain of DGKgamma acts as a nuclear transport signal. Furthermore, to address the function of DGKgamma in the nucleus, we produced stable cell lines of wild-type DGKgamma and mutants, including kinase negative, and investigated their cell size, growth rate, and cell cycle. The cells expressing the kinase-negative mutant of DGKgamma were larger in size and showed slower growth rate, and the S phase of the cells was extended. These findings implicate that nuclear DGKgamma regulates cell cycle.

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  • Identification and characterization of a novel human type II diacylglycerol kinase, DGKκ. 査読

    Imai, S, Kai, M, Yasuda, S, Kanoh, H, Sakane, F

    J. Biol. Chem.   280 ( 48 )   39870 - 39881   2005年12月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1074/jbc.M500669200

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MISC

  • AEBP1は口腔扁平上皮がんにおいて骨格筋細胞分化の抑制因子として働く

    岡崎史佳, 岡崎史佳, 関口翔平, 関口翔平, 萬顕, 萬顕, 新沼猛, 北嶋洋志, 山本英一郎, 甲斐正広, 丸山玲緒, 丸山玲緒, 高野賢一, 宮崎晃亘, 鈴木拓

    日本癌学会学術総会抄録集(Web)   83rd   2024年

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  • 大腸がんにおけるdiacylglycerol kinase zeta遺伝子バリアントのエピジェネティックな制御

    甲斐 正広, 新沼 猛, 北嶋 洋志, 丸山 玲緒, 山本 英一郎, 鈴木 拓

    日本癌学会総会記事   75回   P - 1061   2016年10月

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    記述言語：英語   出版者・発行元：日本癌学会  

    医中誌

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  • 大腸がんのDNAメチル化異常におけるTET1関与の可能性(Possible role of TET1 dysregulation to induce aberrant DNA methylation in colorectal cancer)

    鈴木 拓, 丸山 玲緒, 津矢田 明泰, 新沼 猛, 山本 英一郎, 伊早坂 舞, 甲斐 正広, 篠村 恭久, 今井 浩三

    日本癌学会総会記事   73回   P - 1122   2014年9月

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    記述言語：英語   出版者・発行元：日本癌学会  

    医中誌

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  • DGKGは大腸がん細胞の増殖・浸潤・遊走をその酵素活性によらず抑制する(DGKG attenuates proliferation, invasion and migration of colorectal cancer cells independently of its enzymic activity)

    甲斐 正広, 山本 英一郎, 丸山 玲緒, 佐藤 亜紀子, 新沼 猛, 津矢田 明泰, 鈴木 拓

    日本癌学会総会記事   72回   341 - 341   2013年10月

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    記述言語：英語   出版者・発行元：日本癌学会  

    医中誌

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  • 悪性黒色腫の細胞浸潤におけるDGK-γの関与(DGK-gamma is involved in suppression of malignant melanoma cell invasion)

    佐藤 亜紀子, 甲斐 正広, 鈴木 拓, 山本 英一郎, 丸山 玲緒, 西坂 尚大, 山下 利春

    日本癌学会総会記事   71回   359 - 359   2012年8月

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    記述言語：英語   出版者・発行元：日本癌学会  

    医中誌

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  • Diacylglycerol kinases as emerging potential drug targets for a variety of diseases

    Fumio Sakane, Shin-ichi Imai, Masahiro Kai, Satoshi Yasuda, Hideo Kanoh

    CURRENT DRUG TARGETS   9 ( 8 )   626 - 640   2008年8月

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    記述言語：英語   掲載種別：書評論文，書評，文献紹介等  

    Web of Science

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  • Diacylglycerol kinases: Why so many of them?

    Fumio Sakane, Shin-ichi Imai, Masahiro Kai, Satoshi Yasuda, Hideo Kanoh

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS   1771 ( 7 )   793 - 806   2007年7月

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    記述言語：英語   掲載種別：書評論文，書評，文献紹介等  

    DOI： 10.1016/j.bbalip.2007.04.006

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  • β2-chimaerin のチロシンリン酸化によるRac特異的GAP活性の抑制

    甲斐 正広, 安田 智, 今井 伸一, 坂根 郁夫, 加納 英雄

    脂質生化学研究   49   312 - 315   2007年6月

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    記述言語：日本語  

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  • ジアシルグリセロールキナーゼγは細胞刺激に応答し β2-chimaerin (Rac特異的GAP)を活性化する

    安田 智, 甲斐 正広, 今井 伸一, 坂根 郁夫, 加納 英雄

    脂質生化学研究   49   302 - 304   2007年6月

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    記述言語：日本語  

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  • The plasma membrane translocation of diacylglycerol kinase delta 1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain

    S Imai, M Kai, K Yamada, H Kanoh, F Sakane

    BIOCHEMICAL JOURNAL   382 ( 3 )   957 - 966   2004年9月

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  • Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy

    S Miyamoto, M Hirata, A Yamazaki, T Kageyama, H Hasuwa, H Mizushima, Y Tanaka, H Yagi, K Sonoda, M Kai, H Kanoh, H Nakano, E Mekada

    CANCER RESEARCH   64 ( 16 )   5720 - 5727   2004年8月

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  • Diacylglycerol kinase gamma serves as an upstream suppressor of Rac1 and lamellipodium formation

    S Tsushima, M Kai, K Yamada, S Imai, K Houkin, H Kanoh, F Sakane

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 27 )   28603 - 28613   2004年7月

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  • Differential localization of lipid phosphate phosphatases 1 and 3 to cell surface subdomains in polarized MDCK cells

    YJ Jia, M Kai, Wada, I, F Sakane, H Kanoh

    FEBS LETTERS   552 ( 2-3 )   240 - 246   2003年9月

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  • Cell surface activities of the human type 2b phosphatidic acid phosphatase

    T Ishikawa, M Kai, Wada, I, H Kanoh

    JOURNAL OF BIOCHEMISTRY   127 ( 4 )   645 - 651   2000年4月

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  • Molecular characterization of the type 2 phosphatidic acid phosphatase

    H Kanoh, M Kai, Wada, I

    CHEMISTRY AND PHYSICS OF LIPIDS   98 ( 1-2 )   119 - 126   1999年4月

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  • ホスファチジン酸ホスファターゼ

    蛋白質・核酸・酵素   44   983 - 8   1999年

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  • [Phosphatidic acid phosphatase]

    Tanpakushitsu Kakusan Koso.   44   983 - 8   1999年

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  • Phosphatidic acid phosphatase (type 2), haloperoxidase family and germ cell migration

    Wada, I, M Kai, H Kanoh

    SEIKAGAKU   70 ( 9 )   1183 - 1188   1998年9月

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    記述言語：日本語   掲載種別：書評論文，書評，文献紹介等  

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  • ホスファチジン酸ホスファターゼ２型とハロペルオキシダーゼファミリーと生殖細胞ガイダンス．

    生化学   70   1185 - 8   1998年

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  • Phosphatidic acid phosphatase from mammalian tissues: discovery of channel-like proteins with unexpected functions

    H Kanoh, M Kai, Wada, I

    BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM   1348 ( 1-2 )   56 - 62   1997年9月

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  • Promotion of transferrin folding by cyclic interactions with calnexin and calreticulin

    Wada, I, M Kai, S Imai, F Sakane, H Kanoh

    EMBO JOURNAL   16 ( 17 )   5420 - 5432   1997年9月

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  • Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase

    M Kai, Wada, I, S Imai, F Sakane, H Kanoh

    JOURNAL OF BIOLOGICAL CHEMISTRY   272 ( 39 )   24572 - 24578   1997年9月

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  • Molecular properties of enzymes involved in diacylglycerol and phosphatidate metabolism

    H Kanoh, M Kai, Wada, I

    JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING   14 ( 1-3 )   245 - 250   1996年9月

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  • Translocation of diacylglycerol kinase alpha to the nuclear matrix of rat thymocytes and peripheral T-lymphocytes

    Wada, I, M Kai, S Imai, F Sakane, H Kanoh

    FEBS LETTERS   393 ( 1 )   48 - 52   1996年9月

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  • Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (Type 2) bound to plasma membranes - Polymerase chain reaction amplification of mouse H2O2-inducible hic53 clone yielded the cDNA encoding phosphatidic acid phosphatase

    M Kai, Wada, I, S Imai, F Sakane, H Kanoh

    JOURNAL OF BIOLOGICAL CHEMISTRY   271 ( 31 )   18931 - 18938   1996年8月

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  • Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those the EPH family of protein-tyrosine kinases

    F Sakane, S Imai, M Kai, Wada, I, H Kanoh

    JOURNAL OF BIOLOGICAL CHEMISTRY   271 ( 14 )   8394 - 8401   1996年4月

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  • The C-terminal part of diacylglycerol kinase alpha lacking zinc fingers serves as a catalytic domain.

    Biochem J   318   583 - 90   1996年

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  • LOCALIZATION OF THE GENE ENCODING DIACYLGLYCEROL-KINASE-3 (DAGK3) TO HUMAN-CHROMOSOME 3Q27-28 AND MOUSE CHROMOSOME-16

    J FITZGIBBON, D WELLS, A PILZ, J DELHANTY, M KAI, H KANOH, D HUNT

    CURRENT EYE RESEARCH   14 ( 11 )   1041 - 1043   1995年11月

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    記述言語：英語  

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  • CHAPERONE FUNCTION OF CALRETICULIN WHEN EXPRESSED IN THE ENDOPLASMIC-RETICULUM AS THE MEMBRANE-ANCHORED AND SOLUBLE FORMS

    WADA, I, S IMAI, M KAI, F SAKANE, H KANOH

    JOURNAL OF BIOLOGICAL CHEMISTRY   270 ( 35 )   20298 - 20304   1995年9月

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  • MOLECULAR-CLONING OF A DIACYLGLYCEROL KINASE ISOZYME PREDOMINANTLY EXPRESSED IN HUMAN RETINA WITH A TRUNCATED AND INACTIVE ENZYME EXPRESSION IN MOST OTHER HUMAN-CELLS

    M KAI, F SAKANE, S IMAI, WADA, I, H KANOH

    JOURNAL OF BIOLOGICAL CHEMISTRY   269 ( 28 )   18492 - 18498   1994年7月

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    記述言語：英語  

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共同研究・競争的資金等の研究課題

  • リン脂質代謝酵素の機能解析

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    資金種別：競争的資金

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