研究者詳細

顔写真

カサハラ　アツコ
笠原　敦子
Atsuko Kasahara
所属
大学院生命科学研究科　脳生命統御科学専攻　細胞ネットワーク講座（膜輸送機構解析分野）
職名
助教
学位

  • 博士（理学） （筑波大学）

経歴 3

  • 2016年 ～ 2024年
    金沢大学 がん進展制御研究所

  • 2008年 ～ 2014年
    University of Geneva

  • 2015年 ～
    University of Padua

学歴 3

  • 筑波大学 大学院 生命環境科学研究科 情報生物科学専攻 (博士課程）

    2004年 ～ 2006年

  • 筑波大学 大学院バイオシステム研究科 バイオシステム専攻 (修士課程）

    2002年 ～ 2004年

  • 筑波大学 第二学群 生物学類

    1998年 ～ 2002年

所属学協会 2

  • 日本生化学会

  • 日本ミトコンドリア学会

研究分野 1

  • ライフサイエンス / 細胞生物学 /

論文 18

  1. Lysine-arginine imbalance overcomes therapeutic tolerance governed by the transcription factor E3-lysosome axis in glioblastoma. 国際誌

    Yongwei Jing, Masahiko Kobayashi, Mahmoud I Shoulkamy, Meiqi Zhou, Ha Thi Vu, Hiroshi Arakawa, Hemragul Sabit, Sadahiro Iwabuchi, Cong Quang Vu, Atsuko Kasahara, Masaya Ueno, Yuko Tadokoro, Kenta Kurayoshi, Xi Chen, Yuhang Yan, Satoshi Arai, Shinichi Hashimoto, Tomoyoshi Soga, Tomoki Todo, Mitsutoshi Nakada, Atsushi Hirao

    Nature communications　16　(1)　2876-2876　2025年4月1日

    DOI： 10.1038/s41467-025-56946-z 　

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    Recent advances in cancer therapy have underscored the importance of targeting specific metabolic pathways. In this study, we propose a precision nutrition approach aimed at lysosomal function in glioblastoma multiforme (GBM). Using patient-derived GBM cells, we identify lysosomal activity as a unique metabolic biomarker of tumorigenesis, controlling the efficacy of temozolomide (TMZ), a standard GBM therapy. Employing combined analyses of clinical patient samples and xenograft models, we further elucidate the pivotal role of Transcription Factor Binding To IGHM Enhancer 3 (TFE3), a master regulator of lysosomal biogenesis, in modulating malignant properties, particularly TMZ tolerance, by regulating peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α)-mediated mitochondrial activity. Notably, we find that lysine protects GBM cells from lysosomal stress by counteracting arginine's effects on nitric oxide production. The lysine restriction mimetic, homoarginine administration, significantly enhances the efficacy of anticancer therapies through lysosomal dysfunction. This study underscores the critical role of lysosomal function modulated by amino acid metabolism in GBM pathogenesis and treatment.

  2. Mitochondria in Lung Cancer Progression

    Masafumi Noguchi, Keiko Iwata, Norihito Shintani, Atsuko Kasahara

    Current Pharmacology Reports　2024年8月27日

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1007/s40495-024-00361-3 　

    eISSN：2198-641X

  3. A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite 査読有り

    Masaya Ueno, Hiroki Sugiyama, Feng Li, Tatsuya Nishimura, Hiroshi Arakawa, Xi Chen, Xiaoxiao Cheng, Shinji Takeuchi, Yumie Takeshita, Toshinari Takamura, Sakae Miyagi, Tadashi Toyama, Tomoyoshi Soga, Yusuke Masuo, Yukio Kato, Hiroyuki Nakamura, Hiromasa Tsujiguchi, Akinori Hara, Atsushi Tajima, Moeko Noguchi-Shinohara, Kenjiro Ono, Kenta Kurayoshi, Masahiko Kobayashi, Yuko Tadokoro, Atsuko Kasahara, Mahmoud I. Shoulkamy, Katsuhiro Maeda, Tomoki Ogoshi, Atsushi Hirao

    Analytical Chemistry　96　(36)　14499-14507　2024年8月26日

    出版者・発行元： American Chemical Society (ACS)

    DOI： 10.1021/acs.analchem.4c02653 　

    ISSN：0003-2700

    eISSN：1520-6882

  4. Targeting cis-regulatory elements of FOXO family is a novel therapeutic strategy for induction of leukemia cell differentiation. 国際誌 査読有り

    Kenta Kurayoshi, Yusuke Takase, Masaya Ueno, Kumiko Ohta, Kyoko Fuse, Shuji Ikeda, Takayoshi Watanabe, Yuki Nishida, Shin-Ichi Horike, Kazuyoshi Hosomichi, Yuichi Ishikawa, Yuko Tadokoro, Masahiko Kobayashi, Atsuko Kasahara, Yongwei Jing, Mahmoud I Shoulkamy, Makiko Meguro-Horike, Kensuke Kojima, Hitoshi Kiyoi, Hiroshi Sugiyama, Hiroki Nagase, Atsushi Tajima, Atsushi Hirao

    Cell Death & Disease　14　(9)　642　2023年9月

    DOI： 10.1038/s41419-023-06168-2 　

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    Differentiation therapy has been proposed as a promising therapeutic strategy for acute myeloid leukemia (AML); thus, the development of more versatile methodologies that are applicable to a wide range of AML subtypes is desired. Although the FOXOs transcription factor represents a promising drug target for differentiation therapy, the efficacy of FOXO inhibitors is limited in vivo. Here, we show that pharmacological inhibition of a common cis-regulatory element of forkhead box O (FOXO) family members successfully induced cell differentiation in various AML cell lines. Through gene expression profiling and differentiation marker-based CRISPR/Cas9 screening, we identified TRIB1, a complement of the COP1 ubiquitin ligase complex, as a functional FOXO downstream gene maintaining an undifferentiated status. TRIB1 is direct target of FOXO3 and the FOXO-binding cis-regulatory element in the TRIB1 promoter, referred to as the FOXO-responsive element in the TRIB1 promoter (FRE-T), played a critical role in differentiation blockade. Thus, we designed a DNA-binding pharmacological inhibitor of the FOXO-FRE-T interface using pyrrole-imidazole polyamides (PIPs) that specifically bind to FRE-T (FRE-PIPs). The FRE-PIPs conjugated to chlorambucil (FRE-chb) inhibited transcription of TRIB1, causing differentiation in various AML cell lines. FRE-chb suppressed the formation of colonies derived from AML cell lines but not from normal counterparts. Administration of FRE-chb inhibited tumor progression in vivo without remarkable adverse effects. In conclusion, targeting cis-regulatory elements of the FOXO family is a promising therapeutic strategy that induces AML cell differentiation.

  5. Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line. 国際誌

    Masafumi Noguchi, Susumu Kohno, Anna Pellattiero, Yukino Machida, Keitaro Shibata, Norihito Shintani, Takashi Kohno, Noriko Gotoh, Chiaki Takahashi, Atsushi Hirao, Luca Scorrano, Atsuko Kasahara

    Cell death & disease　14　(4)　241-241　2023年4月5日

    DOI： 10.1038/s41419-023-05768-2 　

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    Drug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line. Accordingly, resistant cells depended on mitochondrial ATP generation, and their mitochondria were elongated with narrower cristae. In the resistant cells, levels of Opa1 were increased and its genetic or pharmacological inhibition reverted the mitochondrial morphology changes and sensitized them to gefitinib-induced cytochrome c release and apoptosis. In vivo, the size of gefitinib-resistant lung orthotopic tumors was reduced when gefitinib was combined with the specific Opa1 inhibitor MYLS22. The combo gefitinib-MYLS22 treatment increased tumor apoptosis and reduced its proliferation. Thus, the mitochondrial protein Opa1 participates in gefitinib resistance and can be targeted to overcome it.

  6. RHEB is a potential therapeutic target in T cell acute lymphoblastic leukemia

    Loc Thi Pham, Hui Peng, Masaya Ueno, Susumu Kohno, Atuso Kasada, Kazuyoshi Hosomichi, Takehiro Sato, Kenta Kurayoshi, Masahiko Kobayashi, Yuko Tadokoro, Atsuko Kasahara, Mahmoud I. Shoulkamy, Bo Xiao, Paul F. Worley, Chiaki Takahashi, Atsushi Tajima, Atsushi Hirao

    Biochemical and Biophysical Research Communications　621　74-79　2022年9月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.bbrc.2022.06.089 　

    ISSN：0006-291X

  7. Therapeutic advantage of targeting lysosomal membrane integrity supported by lysophagy in malignant glioma. 国際誌

    Yongwei Jing, Masahiko Kobayashi, Ha Thi Vu, Atsuko Kasahara, Xi Chen, Loc Thi Pham, Kenta Kurayoshi, Yuko Tadokoro, Masaya Ueno, Tomoki Todo, Mitsutoshi Nakada, Atsushi Hirao

    Cancer science　113　(8)　2716-2726　2022年8月

    DOI： 10.1111/cas.15451 　

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    Lysosomes function as the digestive system of a cell and are involved in macromolecular recycling, vesicle trafficking, metabolic reprogramming, and progrowth signaling. Although quality control of lysosome biogenesis is thought to be a potential target for cancer therapy, practical strategies have not been established. Here, we show that lysosomal membrane integrity supported by lysophagy, a selective autophagy for damaged lysosomes, is a promising therapeutic target for glioblastoma (GBM). In this study, we found that ifenprodil, an FDA-approved drug with neuromodulatory activities, efficiently inhibited spheroid formation of patient-derived GBM cells in a combination with autophagy inhibition. Ifenprodil increased intracellular Ca2+ level, resulting in mitochondrial reactive oxygen species-mediated cytotoxicity. The ifenprodil-induced Ca2+ elevation was due to Ca2+ release from lysosomes, but not endoplasmic reticulum, associated with galectin-3 punctation as an indicator of lysosomal membrane damage. As the Ca2+ release was enhanced by ATG5 deficiency, autophagy protected against lysosomal membrane damage. By comparative analysis of 765 FDA-approved compounds, we identified another clinically available drug for central nervous system (CNS) diseases, amoxapine, in addition to ifenprodil. Both compounds promoted degradation of lysosomal membrane proteins, indicating a critical role of lysophagy in quality control of lysosomal membrane integrity. Importantly, a synergistic inhibitory effect of ifenprodil and chloroquine, a clinically available autophagy inhibitor, on spheroid formation was remarkable in GBM cells, but not in nontransformed neural progenitor cells. Finally, chloroquine dramatically enhanced effects of the compounds inducing lysosomal membrane damage in a patient-derived xenograft model. These data demonstrate a therapeutic advantage of targeting lysosomal membrane integrity in GBM.

  8. Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner. 国際誌

    Naho Nomura, Chiaki Ito, Takako Ooshio, Yuko Tadokoro, Susumu Kohno, Masaya Ueno, Masahiko Kobayashi, Atsuko Kasahara, Yusuke Takase, Kenta Kurayoshi, Sha Si, Chiaki Takahashi, Masaaki Komatsu, Toru Yanagawa, Atsushi Hirao

    Scientific reports　11　(1)　1666-1666　2021年1月18日

    DOI： 10.1038/s41598-021-81076-z 　

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    Autophagy is a cellular degradation system contributing to homeostasis of tissue stem cells including haematopoietic stem cells (HSCs). It plays pleiotropic roles in HSC characteristics throughout life, but its stage-specific roles in HSC self-renewal are unclear. To investigate the effects of Atg5 deletion on stage-specific HSC functions, we compared the repopulating capacity of HSCs in Atg5f/f;Vavi-cre mice from postnatal day (P) 0-7 weeks of age. Interestingly, Atg5 deficiency led to no remarkable abnormality in the HSC self-renewal capacity at P0, but significant defects at P7, followed by severe defects. Induction of Atg5 deletion at P5 by tamoxifen administration to Atg5f/f;Rosa26-Cre-ERT2 mice resulted in normal haematopoiesis, including the HSC population, until around 1 year, suggesting that Atg5 in the early neonatal period was critical for haematopoiesis in adults. Mitochondrial oxidative stress was increased by Atg5 loss in neonatal HSC/progenitor cells. Although p62 had accumulated in immature bone marrow cells of Atg5f/f;Vavi-cre mice, p62 deletion did not restore defective HSC functions, indicating that Atg5-dependent haematopoietic regulation in the developmental period was independent of p62. This study proposes a critical role of autophagy in HSC protection against harsh environments in the early neonatal stage, which is essential for healthy long-term haematopoiesis.

  9. Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples

    Masaya Ueno, Takuya Tomita, Hiroshi Arakawa, Takahiro Kakuta, Tada-aki Yamagishi, Jumpei Terakawa, Takiko Daikoku, Shin-ichi Horike, Sha Si, Kenta Kurayoshi, Chiaki Ito, Atsuko Kasahara, Yuko Tadokoro, Masahiko Kobayashi, Tsutomu Fukuwatari, Ikumi Tamai, Atsushi Hirao, Tomoki Ogoshi

    Communications Chemistry　3　(1)　2020年12月

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1038/s42004-020-00430-w 　

    eISSN：2399-3669

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    <title>Abstract</title>Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide <italic>N</italic>-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10−6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples.

  10. Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas. 国際誌 査読有り

    Ha Thi Vu, Masahiko Kobayashi, Ahmed M Hegazy, Yuko Tadokoro, Masaya Ueno, Atsuko Kasahara, Yusuke Takase, Naho Nomura, Hui Peng, Chiaki Ito, Yasushi Ino, Tomoki Todo, Mitsutoshi Nakada, Atsushi Hirao

    Cancer science　109　(8)　2497-2508　2018年8月

    DOI： 10.1111/cas.13695 　

    ISSN：1347-9032

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    Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells' responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from patients with glioblastoma. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy. Screening of an anticancer drug library identified compounds that showed greater efficacy to ATG5-knockout glioma cells compared to control. While several selected compounds, including nigericin and salinomycin, remarkably induced autophagy, potent autophagy inducers by mTOR inhibition did not exhibit the ATG5-dependent cytoprotective effects. Nigericin in combination with ATG5 deficiency synergistically suppressed spheroid formation by glioma cells in a manner mitigated by Ca2+ chelation or CaMKK inhibition, indicating that, in combination with autophagy inhibition, calcium-mobilizing compounds contribute to efficient anticancer therapeutics. ATG5-knockout cells treated with nigericin showed increased mitochondria-derived reactive oxygen species and apoptosis compared to controls, indicating that autophagy protects glioma cells from mitochondrial reactive oxygen species-mediated damage. Finally, using a patient-derived xenograft model, we demonstrated that chloroquine, a pharmacological autophagy inhibitor, dramatically enhanced the efficacy of compounds selected in this study. Our findings propose a novel therapeutic strategy in which calcium-mobilizing compounds are combined with autophagy inhibitors to treat patients with glioblastoma.

  11. Mitochondrial dynamics coordinate cell differentiation 査読有り

    Masafumi Noguchi, Atsuko Kasahara

    Biochemical and Biophysical Research Communications　500　(1)　59-64　2018年5月27日

    出版者・発行元： Elsevier B.V.

    DOI： 10.1016/j.bbrc.2017.06.094 　

    ISSN：1090-2104 0006-291X

  12. ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells 査読有り

    Esen Yonca Bassoy, Atsuko Kasahara, Valentina Chiusolo, Guillaume Jacquemin, Emma Boydell, Sebastian Zamorano, Cristina Riccadonna, Serena Pellegatta, Nicolas Hulo, Valerie Dutoit, Madiha Derouazi, Pierre Yves Dietrich, Paul R. Walker, Denis Martinvalet

    EMBO JOURNAL　36　(11)　1493-1512　2017年6月

    DOI： 10.15252/embj.201695429 　

    ISSN：0261-4189

    eISSN：1460-2075

  13. Granzyme B-induced mitochondrial ROS are required for apoptosis 査読有り

    G. Jacquemin, D. Margiotta, A. Kasahara, E. Y. Bassoy, M. Walch, J. Thiery, J. Lieberman, D. Martinvalet

    CELL DEATH AND DIFFERENTIATION　22　(5)　862-874　2015年4月

    DOI： 10.1038/cdd.2014.180 　

    ISSN：1350-9047

    eISSN：1476-5403

  14. Mitochondria: from cell death executioners to regulators of cell differentiation 査読有り

    Atsuko Kasahara, Luca Scorrano

    TRENDS IN CELL BIOLOGY　24　(12)　761-770　2014年12月

    DOI： 10.1016/j.tcb.2014.08.005 　

    ISSN：0962-8924

  15. Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling. 査読有り

    Kasahara A, Cipolat S, Chen Y, Dorn GW, Scorrano L

    Science (New York, N.Y.)　342　(6159)　734-737　2013年11月

    DOI： 10.1126/science.1241359 　

    ISSN：0036-8075

  16. Normal mitochondrial respiratory function is essential for spatial remote memory in mice 査読有り

    Daisuke Tanaka, Kazuto Nakada, Keizo Takao, Emi Ogasawara, Atsuko Kasahara, Akitsugu Sato, Hiromichi Yonekawa, Tsuyoshi Miyakawa, Jun-Ichi Hayashi

    MOLECULAR BRAIN　1　21　2008年

    DOI： 10.1186/1756-6606-1-21 　

    ISSN：1756-6606

  17. Deletion-mutant mtDNA increases in somatic tissues but decreases in female germ cells with age 査読有り

    Akitsugu Sato, Kazuto Nakada, Hiroshi Shitara, Atsuko Kasahara, Hiromichi Yonekawa, Jun-Ichi Hayashi

    GENETICS　177　(4)　2031-2037　2007年12月

    DOI： 10.1534/genetics.107.081026 　

    ISSN：0016-6731

  18. [Mutagens inducing mutations in mammalian mitochondrial DNA]. 査読有り

    Watanabe N, Kasahara A, Nakada K, Hayashi J

    Nihon rinsho. Japanese journal of clinical medicine　60 Suppl 4　35-38　2002年4月

    ISSN：0047-1852

︎全件表示 ︎最初の5件までを表示

MISC 7

  1. Generation of trans-mitochondrial mice carrying homoplasmic mtDNA with a missense mutation in a structural gene using ES cells

    Atsuko Kasahara, Jun-Ichi Hayashi

    NEUROMUSCULAR DISORDERS　16　S58-S58　2006年7月

    ISSN： 0960-8966

  2. Generation of trans-mitochondrial mice carrying homoplasmic mtDNAs with a missense mutation in a structural gene using ES cells 国際誌

    A Kasahara, K Ishikawa, M Yamaoka, M Ito, N Watanabe, M Akimoto, A Sato, K Nakada, H Endo, Y Suda, S Aizawa, JI Hayashi

    HUMAN MOLECULAR GENETICS　15　(6)　871-881　2006年3月

    DOI： 10.1093/hmg/ddl005 　

    ISSN： 0964-6906

  3. Generation of trans-mitochondrial mice carrying homoplasmic mtDNAs with a missense mutation in a structural gene using ES cells

    A Kasahara, K Ishikawa, M Yamaoka, M Ito, N Watanabe, M Akimoto, A Sato, K Nakada, H Endo, Y Suda, S Aizawa, JI Hayashi

    HUMAN MOLECULAR GENETICS　15　(6)　871-881　2006年3月

    DOI： 10.1093/hmg/ddl005 　

    ISSN： 0964-6906

  4. Application of ES cells for generation of respiration-deficient mice carrying mtDNA with a large-scale deletion 国際誌

    K Ishikawa, A Kasahara, N Watanabe, K Nakada, A Sato, Y Suda, S Aizawa, JI Hayashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　333　(2)　590-595　2005年7月

    DOI： 10.1016/j.bbrc.2005.05.155 　

    ISSN： 0006-291X

  5. Application of ES cells for generation of respiration-deficient mice carrying mtDNA with a large-scale deletion

    K Ishikawa, A Kasahara, N Watanabe, K Nakada, A Sato, Y Suda, S Aizawa, JI Hayashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　333　(2)　590-595　2005年7月

    DOI： 10.1016/j.bbrc.2005.05.155 　

    ISSN： 0006-291X

  6. Accumulation of pathogenic ΔmtDNA induced deafness but not diabetic phenotypes in mito-mice.

    NAKADA K, SATO A, SONE H, KASAHARA A, IKEDA K, KAGAWA Y, YONEKAWA H, HAYASHI J

    Biochem. Biophys. Res. Commun.　323　(1)　175-184　2004年10月

    DOI： 10.1016/j.bbrc.2004.08.073 　

    ISSN： 0006-291X

  7. Accumulation of pathogenic Delta mtDNA induced deafness but not diabetic phenotypes in mito-mice

    K Nakada, A Sato, H Sone, A Kasahara, K Ikeda, Y Kagawa, H Yonekawa, J Hayashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　323　(1)　175-184　2004年10月

    DOI： 10.1016/j.bbrc.2004.08.073 　

    ISSN： 0006-291X

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 5

  1. 細胞運命決定におけるオルガネラ接触部位制御メカニズムの解明

    笠原 敦子

    2024年4月1日 ～ 2027年3月31日

  2. がん幹細胞性におけるミトコンドリア動態の果たす役割を明らかにする

    笠原 敦子

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (C)

    研究機関：Kanazawa University

    2019年4月1日 ～ 2022年3月31日

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    ミトコンドリアの多彩な機能に関わる形態を制御する因子が、がん細胞の悪性形質の獲得や維持にどのように関与しているかを明らかにすることを目的とした。分子標的薬耐性肺がん細胞はミトコンドリア融合因子OPA1発現上昇によりその耐性を維持しており、OPA1の阻害により薬剤耐性が解除されることを示した。がん細胞は正常細胞に比べ、ミトコンドリア形態変化によるカルシウム制御が異なることを観察した。一方で、ミトコンドリア動態制御因子が悪性形質に関与することが報告されているグリオーマ細胞や、分子標的薬耐性肺がん細胞のミトコンドリア動態制御因子の発現を制御する上流因子の同定には至らなかった。

  3. がん悪性化におけるミトコンドリア逆行性制御の解明

    笠原 敦子

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Young Scientists (B)

    研究機関：Kanazawa University

    2017年4月1日 ～ 2019年3月31日

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    悪性度の高い脳腫瘍である膠芽腫（グリオブラストーマ）では、放射線・化学療法に対して耐性を持ち、転移や再発の直接の原因となる、がん幹細胞様集団が見出されている。本研究では、このがん幹細胞様集団特異的なミトコンドリアの形態や細胞内局在を見出した。この特異的なミトコンドリア動態が、細胞表面のグリコカリックス発現を制御し、細胞障害性Tリンパ球によるグリオブラストーマ幹細胞様集団の細胞認識・傷害に関与していることを明らかにした。

  4. ‐ 競争的資金

  5. - 競争的資金