論文 - 末松　誠

PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth

Morita M., Sato T., Nomura M., Sakamoto Y., Inoue Y., Tanaka R., Ito S., Kurosawa K., Yamaguchi K., Sugiura Y., Takizaki H., Yamashita Y., Katakura R., Sato I., Kawai M., Okada Y., Watanabe H., Kondoh G., Matsumoto S., Kishimoto A., Obata M., Matsumoto M., Fukuhara T., Motohashi H., Suematsu M., Komatsu M., Nakayama K.I., Watanabe T., Soga T., Shima H., Maemondo M., Tanuma N.

Cancer Cell （Cancer Cell）  33 （ 3 ） 355 - 367.e7 2018年03月

ISSN  15356108

　概要を見る

© 2018 Elsevier Inc. Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D-induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy. Importantly, we observed that pulmonary neuroendocrine tumors (NETs), including small-cell lung cancer (SCLC), express PKM1, and that PKM1 expression is required for SCLC cell proliferation. Our findings provide a rationale for targeting PKM1 therapeutically in certain cancer subtypes, including pulmonary NETs. The relative importance of PKM isoforms in tumor growth has been controversial. Morita et al. show that PKM1 promotes the growth of multiple tumor models using mouse lines expressing PKM1 or PKM2 from the endogenous Pkm locus. PKM1 is expressed in human SCLC, and it is important for SCLC cell proliferation.

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Utilizing mass spectrometry imaging to map the thyroid hormones triiodothyronine and thyroxine in Xenopus tropicalis tadpoles

Goto-Inoue N., Sato T., Morisasa M., Kashiwagi A., Kashiwagi K., Sugiura Y., Sugiyama E., Suematsu M., Mori T.

Analytical and Bioanalytical Chemistry （Analytical and Bioanalytical Chemistry）  410 （ 4 ） 1333 - 1340 2018年02月

ISSN  16182642

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© 2017, Springer-Verlag GmbH Germany, part of Springer Nature. Thyroid hormones are not only responsible for thermogenesis and energy metabolism in animals, but also have an important role in cell differentiation and development. Amphibian metamorphosis provides an excellent model for studying the remodeling of the body. This metamorphic organ remodeling is induced by thyroid hormones, and a larval body is thus converted into an adult one. The matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) imaging technology is expected to be a suitable tool for investigating small bioreactive molecules. The present study describes the distribution of the thyroid hormones, i.e., triiodothyronine (T3) and thyroxine (T4) and their inactive form reverse T3 (rT3) in Xenopus tropicalis tadpoles using two different types of imaging techniques, MS/MS and Fourier transform (FT)-MS imaging. As a result of MS/MS imaging, we demonstrated that T3 was mainly distributed in the gills. T4 was faintly localized in the eyes, inner gills, and intestine during metamorphosis. The intensity of T3 in the gills and the intensity of T4 in the body fluids were increased during metamorphosis. Moreover, the localization of the inactive form rT3 was demonstrated to be separate from T3, namely in the intestine and muscles. In addition, FT-MS imaging could utilize simultaneous imaging including thyroid hormone. This is the first report to demonstrate the molecular distribution of thyroid hormones themselves and to discriminate T3, T4, and rT3 in animal tissues.

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Plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites

Andrabi S.B.A., Tahara M., Matsubara R., Toyama T., Aonuma H., Sakakibara H., Suematsu M., Tanabe K., Nozaki T., Nagamune K.

Parasitology International （Parasitology International）  67 （ 1 ） 47 - 58 2018年02月

ISSN  13835769

　概要を見る

© 2017 The Authors Cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. Here, we show that the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. Cytokinins regulate the growth and cell cycle progression of T. gondii by mediating expression of the cyclin gene TgCYC4. A natural form of cytokinin, trans-zeatin (t-zeatin), upregulated expression of this cyclin, while a synthetic cytokinin, thidiazuron, downregulated its expression. Immunofluorescence microscopy and quantitative PCR analysis showed that t-zeatin increased the genome-copy number of apicoplast, which are non-photosynthetic plastid, in the parasite, while thidiazuron led to their disappearance. Thidiazuron inhibited growth of T. gondii and Plasmodium falciparum, a human malaria parasite, suggesting that thidiazuron has therapeutic potential as an inhibitor of apicomplexan parasites.

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Future of Rare Diseases Research 2017–2027: An IRDiRC Perspective

Austin C.P., Cutillo C.M., Lau L.P.L., Jonker A.H., Rath A., Julkowska D., Thomson D., Terry S.F., de Montleau B., Ardigò D., Hivert V., Boycott K.M., Baynam G., Kaufmann P., Taruscio D., Lochmüller H., Suematsu M., Incerti C., Draghia-Akli R., Norstedt I., Wang L., Dawkins H.J.S.

Clinical and Translational Science （Clinical and Translational Science）  11 （ 1 ） 21 - 27 2018年01月

ISSN  17528054

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Identification of outer mitochondrial membrane cytochrome b₅ as a modulator for androgen synthesis in leydig cells

Ogishima Tadashi, Kinoshita Junya, Mitani Fumiko, Suematsu Makoto, Ito Aki

Journal of biological chemistry 278 （ 23 ） 21204-21211 2003年06月

研究論文（学術雑誌）, 共著

An Inverse Correlation between Expression of a Preprocathepsin B-related Protein with Cysteine-rich Sequences and Steroid 11beta-Hydroxylase in Adrenocortical Cells

Mukai Kuniaki, Mitani Fumiko, Nagasawa Hideko, Suzuki Reiko, Suzuki Tsuneharu, Suematsu Makoto, Ishimura Yuzuru

Journal of biological chemistry 278 （ 19 ） 17084-17092 2003年05月

研究論文（学術雑誌）, 共著

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Kajimura Mayumi, Shimoyama Masaru, Tsuyama Shingo, Suzuki Tsuneharu, Kozaki Shinji, Takenaka Shingo, Tsubota Kazuo, Oguchi Yoshihisa, Suematsu Makoto

FASEB journal 17 （ 3 ） 506-508 2003年03月

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Peyer’s patch is the essential site in initiating murine acute and lethal graft-versus-host reaction

Murai Masako, Yoneyama Hiroyuki, Ezaki Taichi, Suematsu Makoto, Terashima Yuya, Harada Akihisa, Hamada Hiromasa, Asakura Hitoshi, Ishikawa Hiromichi, Matsushima Kouji

Nature immunology 4 （ 2 ） 154-160 2003年02月

研究論文（学術雑誌）, 共著

The undifferentiated cell zone is a stem cell zone in adult rat adrenal cortex

Mitani Fumiko, Mukai Kuniaki, Miyamoto H, Suematsu Makoto, Ishimura Yuzuru

Biochimica biophysica acta 1619 （ 3 ） 317-324 2003年02月

研究論文（学術雑誌）, 共著

Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging

Tsuchida Eishun, Komatsu Teruyuki, Matsukawa Yasuko, Nakagawa Akito, Sakai Hiromi, Kobayashi Koichi, Suematsu Makoto

J Journal of biomedical materials research 64A （ 2 ） 257-261 2003年02月

研究論文（学術雑誌）, 共著

Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction

Murai Masako, Yoneyama Hiroyuki, Ezaki Taichi, Suematsu Makoto, Terashima Yuya, Harada Akihisa, Hamada Hiromasa, Asakura Hitoshi, Ishikawa Hiromichi, Matsushima Kouji

Nature immunology 4 （ 2 ） 154-160 2003年02月

研究論文（学術雑誌）, 共著

Expression of heme oxygenase-1 in rat ontogeny.

末松 誠

Arch. Histol. Cytol. 66 （ 1 ） 155-162 2003年

研究論文（学術雑誌）, 単著

Human serum albumin incorporating synthetic heme: Red blood cell substitute without hypertension by nitric oxide scavenging.

末松 誠

J Biomed Mater Res. 64 （ A ） 257-261 2003年

研究論文（学術雑誌）, 単著

Subendothelial dome of gut Peyer’s patches is the essential anatomical site in initiating acute graft-versus-host disease.

末松 誠

Nat. Immunol. 4 （ 1 ） 154-160 2003年

研究論文（学術雑誌）, 単著

The undifferentiated cell zone is a stem cell zone in adult rat adrenal cortex.

末松 誠

Biochim Biophys Acta. 1619 （ 1 ） 317-324 2003年

研究論文（学術雑誌）, 単著

An inverse correlation between expression of a preprocathepsin B-related protein with cysteine-rich sequences and steroid 11-hydroxylase in adrenocortical cells.

末松 誠

J. Biol. Chem. 278 （ 1 ） 17084-17092 2003年

研究論文（学術雑誌）, 単著

Identification of outer mitochondrial membrane cytochrome b5 as a modulator for androgen synthesis in Leydig cells.

末松 誠

J. Biol. Chem. 278 （ 1 ） 21204-21211 2003年

研究論文（学術雑誌）, 単著

Bilirubin rinse: A simple protectant against the rat liver graft injury mimicking heme oxygenase-1 preconditioning.

末松 誠

Hepatology 38 （ 1 ） 364-373 2003年

研究論文（学術雑誌）, 単著

Suppressed apoptosis in the inflamed gastric mucosa of Helicobacter pylori-colonized iNOS-knockout mice.

末松 誠

Free Radic. Biol. Med. 34 （ 1 ） 121-1630 2003年

研究論文（学術雑誌）, 単著

Quartet signal transducers in gas biology.

末松 誠

Antioxid. Redox Signal. 5 （ 1 ） 435-437 2003年

研究論文（学術雑誌）, 単著