研究者詳細 - 阪口　政清

NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions 査読国際誌

Hitoshi Murata, Hitoshi Takamatsu, Sulai Lie, Ken Kataoka, Nam-ho Huh, Masakiyo Sakaguchi

PLoS One 10 ( 11 ) e0142438 2015年11月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PUBLIC LIBRARY SCIENCE

Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson's disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival.

DOI： 10.1371/journal.pone.0142438

REIC/Dkk-3遺伝子治療の胸部悪性腫瘍に対する免疫刺激を介する抗腫瘍効果

諏澤憲, 枝園和彦, 阪口政清, 渡部昌実, 橋田真輔, 宗淳一, 山本寛斉, 牧祐歩, 佃和憲, 那須保友, 公文裕巳, 三好新一郎, 豊岡伸一

日本癌学会総会記事 74回 J - 1224 2015年10月

T790M変異を含むEGFR遺伝子変異を有する非小細胞肺癌細胞株に対するTAE226の抗腫瘍効果

山本寛斉, 阪口政清, 宗淳一, 佃和憲, 木浦勝行, 猶本良夫, 三好新一郎, 豊岡伸一

日本癌学会総会記事 74回 P - 2193 2015年10月

TAE226, a Bis-Anilino Pyrimidine Compound, Shows Anti-Tumor Effect on EGFR-Mutant Non-Small Cell Lung Cancer Cells including T790M Mutant 査読

Hiromasa Yamamoto, Hiroki Otani, Munenori Takaoka, Masakiyo Sakaguchi, Junichi Soh, Masaru Jida, Tsuyoshi Ueno, Takafumi Kubo, Hiroaki Asano, Kazunori Tsukuda, Katsuyuki Kiura, Shinji Hatakeyama, Eiji Kawahara, Yoshio Naomoto, Shinichiro Miyoshi, Shinichi Toyooka

JOURNAL OF THORACIC ONCOLOGY 10 ( 9 ) S311 - S312 2015年9月

Distant Bystander Effect of REIC/Dkk-3 Gene Therapy through Immune System Stimulation in a Murine Model of Thoracic Malignancies 査読

Ken Suzawa, Kazuhiko Shien, Peng Huang, Masakiyo Sakaguchi, Masami Watanabe, Shinsuke Hashida, Junichi Soh, Hiromasa Yamamoto, Yuho Maki, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka

JOURNAL OF THORACIC ONCOLOGY 10 ( 9 ) S599 - S599 2015年9月

Anti-tumor effect of afatinib, an irreversible EGFR/HER2 dual inhibitor, in lung cancers harboring HER2 oncogene 査読

Ken Suzawa, Shinichi Toyooka, Masakiyo Sakaguchi, Tomoaki Ohtsuka, Mototsugu Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi

CANCER RESEARCH 75 2015年8月

Identification of a novel binding protein playing a critical role in HER2 activation in lung cancer cells 査読

Tomoaki Ohtsuka, Masakiyo Sakaguchi, Katsuyoshi Takata, Shinsuke Hashida, Mototsugu Watanabe, Ken Suzawa, Yuho Maki, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka

CANCER RESEARCH 75 2015年8月

Novel germline G660D mutation in HER2 gene detected by whole-exome sequencing can predispose a patient to developing familial lung adenocarcinoma 査読

Hiromasa Yamamoto, Koichiro Higasa, Masakiyo Sakaguchi, Kazuhiko Shien, Junichi Soh, Koichi Ichimura, Masashi Furukawa, Shinsuke Hashida, Kazunori Tsukuda, Nagio Takigawa, Keitaro Matsuo, Katsuyuki Kiura, Sinichiro Miyoshi, Fumihiko Matsuda, Shinichi Toyooka

CANCER RESEARCH 74 ( 19 ) 2014年10月

家族性・孤発性肺腺癌におけるHER2膜貫通領域の新規遺伝子変異(Novel functional mutations in the transmembrane domain of HER2 gene in familial and sporadic lung adenocarcinomas)

山本寛斉, 日笠幸一郎, 阪口政清, 枝園和彦, 宗淳一, 市村浩一, 佃和憲, 瀧川奈義夫, 松尾恵太郎, 木浦勝行, 三好新一郎, 松田文彦, 豊岡伸一

日本癌学会総会記事 73回 E - 2012 2014年9月

新規HER2膜貫通部領域遺伝子変異の機能解析(Novel HER2 mutations in transmembrane dmain result in constitutive autophosphorylation of HER2)

諏澤憲, 阪口政清, 山本寛斉, 宗淳一, 牧佑歩, 橋田真輔, 大塚智昭, 渡邉元嗣, 浅野博昭, 佃和憲, 三好新一郎, 豊岡伸一

日本癌学会総会記事 73回 P - 1328 2014年9月

がんマーカー、サイトケラチン19(CK19)機能の新展開 HER2活性化におけるCK19の役割(Critical role of Cytokeratin-19 in an oncogenic activation of HER2)

大塚智昭, 阪口政清, 渡邉元嗣, 諏澤憲, 橋田真輔, 牧佑歩, 山本寛斉, 宗淳一, 浅野博昭, 佃和憲, 三好新一郎, 豊岡伸一

日本癌学会総会記事 73回 E - 2071 2014年9月

Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells 査読

I. Made Winarsa Ruma, Endy Widya Putranto, Eisaku Kondo, Risayo Watanabe, Ken Saito, Yusuke Inoue, Ken-Ichi Yamamoto, Susumu Nakata, Masaji Kaihata, Hitoshi Murata, Masakiyo Sakaguchi

INTERNATIONAL JOURNAL OF ONCOLOGY 45 ( 1 ) 209 - 218 2014年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPANDIDOS PUBL LTD

Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3 beta activation, while p38 alpha phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with downregulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors.

DOI： 10.3892/ijo.2014.2397

Dramatic Increase in Expression of a Transgene by Insertion of Promoters Downstream of the Cargo Gene 査読国際誌

Masakiyo Sakaguchi, Masami Watanabe, Rie Kinoshita, Haruki Kaku, Hideo Ueki, Junichiro Futami, Hitoshi Murata, Yusuke Inoue, Shun-Ai Li, Peng Huang, Endy Widya Putranto, I. Made Winarsa Ruma, Yasutomo Nasu, Hiromi Kumon, Nam-ho Huh

MOLECULAR BIOTECHNOLOGY 56 ( 7 ) 621 - 630 2014年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：HUMANA PRESS INC

For expression of genes in mammalian cells, various vectors have been developed using promoters including CMV, EF-1 alpha, and CAG promoters and have been widely used. However, such expression vectors sometimes fail to attain sufficient expression levels depending on the nature of cargo genes and/or on host cell types. In the present study, we aimed to develop a potent promoter system that enables high expression levels of cargo genes ubiquitously in many different cell types. We found that insertion of an additional promoter downstream of a cargo gene greatly enhanced the expression levels. Among the constructs we tested, C-TSC cassette (C: CMV-RU5' located upstream; TSC: another promoter unit composed of triple tandem promoters, hTERT, SV40, and CMV, located downstream of the cDNA plus a polyadenylation signal) had the most potent capability, showing far higher efficiency than that of potent conventional vector systems. The results indicate that the new expression system is useful for production of recombinant proteins in mammalian cells and for application as a gene therapeutic measure.

DOI： 10.1007/s12033-014-9738-0

S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells 査読

Jyoti K. Jaiswal, Stine P. Lauritzen, Luana Scheffer, Masakiyo Sakaguchi, Jakob Bunkenborg, Sanford M. Simon, Tuula Kallunki, Marja Jaattela, Jesper Nylandsted

NATURE COMMUNICATIONS 5 3795 2014年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Cell migration and invasion require increased plasma membrane dynamics and ability to navigate through dense stroma, thereby exposing plasma membrane to tremendous physical stress. Yet, it is largely unknown how metastatic cancer cells acquire an ability to cope with such stress. Here we show that S100A11, a calcium-binding protein upregulated in a variety of metastatic cancers, is essential for efficient plasma membrane repair and survival of highly motile cancer cells. Plasma membrane injury-induced entry of calcium into the cell triggers recruitment of S100A11 and Annexin A2 to the site of injury. We show that S100A11 in a complex with Annexin A2 helps reseal the plasma membrane by facilitating polymerization of cortical F-actin and excision of the damaged part of the plasma membrane. These data reveal plasma membrane repair in general and S100A11 and Annexin A2 in particular as new targets for the therapy of metastatic cancers.

DOI： 10.1038/ncomms4795