Exploring the mitochondrial retrograde control in malignant progression

• Project/Area Number: 17K17758
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology; Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: KASAHARA Atsuko 金沢大学, がん進展制御研究所, 助教 (00447244)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ミトコンドリア動態 / カルシウム制御 / カルシウム調節

Outline of Final Research Achievements

Glioblastoma (GBM) is a very aggressive and destructive brain tumour. Numerous studies have identified a tumour cell population in GBM that can initiate glioma development, as glioma stem-like cells. We observed the specific mitochondrial shape, and intracellular localisation in glioma stem-like cells, that regulates sialylated glycan expressions at the plasma membrane, which directly influences the physiological contact, and killing efficiency of cytotoxic T lymphocyte to the glioma stem-like cells.

Academic Significance and Societal Importance of the Research Achievements

これまでがん細胞では、エネルギー代謝制御におけるミトコンドリアの役割が注目・研究されてきた。本研究では、ミトコンドリアの形態や細胞内局在が、がん細胞の悪性形質を制御し、がん免疫療法の効率に関わることを初めて明らかにした。本研究の成果は、悪性がん細胞特異的なミトコンドリア動態が、治療標的となりうる可能性を示唆し、新規のがん治療研究への布石となったと考えている。

Research Products

• [Int'l Joint Research] パドヴァ大学(イタリア)
• [Int'l Joint Research] パドヴァ大学(イタリア)
• [Journal Article] Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas. (2018)
  • Author(s): Vu HT, Kobayashi M, Hegazy AM, Tadokoro Y, Ueno M, Kasahara A, Takase Y, Nomura N, Peng H, Ito C, Ino Y, Todo T, Nakada M, Hirao A
  • Journal Title: Cancer Science Volume: 109 Issue: 8 Pages: 2497-2508
  • DOI: 10.1111/cas.13695
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial dynamics coordinate cell differentiation (2017)
  • Author(s): Noguchi Masafumi, Kasahara Atsuko
  • Journal Title: Biochem Biophys Res Commun Volume: 500 Issue: 1 Pages: 59-64
  • DOI: 10.1016/j.bbrc.2017.06.094
  • Int'l Joint Research
• [Journal Article] ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells (2017)
  • Author(s): Bassoy Esen Yonca, Kasahara Atsuko, Chiusolo Valentina, Jacquemin Guillaume, Boydell Emma, Zamorano Sebastian, Riccadonna Cristina, Pellegatta Serena, Hulo Nicolas、Dutoit Valerie, Derouazi Madiha, Dietrich Pierre Yves, Walker Paul R, Martinvalet Denis
  • Journal Title: EMBO J Volume: 36 Issue: 11 Pages: 1493-1512
  • DOI: 10.15252/embj.201695429
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Mitochondrial dynamics in geftinib-resistant lung adenocarcinoma cells (2018)
  • Author(s): Kasahara A., Noguchi N., Shibata K., Kohno S., Takahashi C., Gotoh N., Kohno T., Scorrano L., Hirao A
  • Organizer: Keystone Symposia Conference, Mitochondrial Biology
  • Int'l Joint Research
• [Presentation] Mitochondrial dynamics in tumour malignancies: retrograde control from mitochondria (2017)
  • Author(s): Atsuko Kasahara
  • Organizer: International Workshop on Mitochondrial Dynamics
  • Int'l Joint Research / Invited
• [Presentation] Mitochondrial dynamics and functions in lung adenocarcinoma cells (2017)
  • Author(s): Noguchi M., Kohno S., Takahashi C., Gotoh N., Kohno T., Hirao A., Scorrano L., Kasahara A
  • Organizer: Padua-Mit-Innsbruck “Mitochondrial Conference
  • Int'l Joint Research
• [Presentation] Mitochondrial dynamics in geftinib-resistant lung adenocarcinoma cells (2017)
  • Author(s): Kasahara A., Noguchi M., Kohno S., Takahashi C., Gotoh N., Kohno T., Scorrano L., Hirao A
  • Organizer: EMBO-FEBS Lecture Course “Mitochondria in life, death and disease”
  • Int'l Joint Research