Roles of acetylated HMGB1 secreted from cancer cells in CRPC
| Project/Area Number |
20K18142
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
Goto Keisuke 広島大学, 病院(医), 助教 (30784251)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | HMGB1 / Prostate cancer / Cancer microenvironment / 前立腺癌 / FGFファミリー / 内分泌療法 / 細胞生物学 |
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| Outline of Research at the Start |
多くの進行性前立腺がん症例に対する内分泌療法において、去勢抵抗性獲得は大きな問題である。去勢抵抗性前立腺がんの詳細な分子機構には未だ不明な点が多い。HMGB1はDNAの安定化に関わる核蛋白であるが、アセチル化により細胞外へ分泌されがんの増殖・浸潤・転移を促進させることが知られている。HMGB1の局在変化が前立腺がんの悪性化に関係すると想定され、その先の去勢抵抗性獲得と関係する可能性がある。本研究では以下に示す方法からアセチル化HMGB1による去勢抵抗性獲得の分子機構の解明を通じて前立腺がんの新たな診断・治療法開発を目指す。
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| Outline of Final Research Achievements |
High mobidity group protein box 1 (HMGB1), a non-histone chromatin binding protein, is normally present in the nucleus. Under certain conditions, HMGB1 is in the cytoplasm and secreted into the extracellular space as the signal molecule. Overexpression of HMGB1 was significantly associated with pT stage, Gleason score. The patients with higher cytoplasmic HMGB1 had significantly worse prognosis after radical prostatectomy. HMGB1 silencing significantly reduced cell proliferation in PCa cells. To assess roles of secreted HMGB1 in cancer microenvironment, HMGB1 levels in periprostatic adipose tissue (PPAT) in patients who underwent radical prostatectomy was investigated. HMGB1 levels in PPAT were significantly higher in cases with higher Gleason score. These results suggested that HMGB1 was associated with PCa progression and cell proliferation, and secreted HMGB1 in cancer microenvironment had significant roles in PCa progression.
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| Academic Significance and Societal Importance of the Research Achievements |
前立腺周囲脂肪組織中のサイトカインの発現が前立腺癌の悪性度と関連することはこれまでにない発見であり、前立腺癌におけるがん微小環境との関連を明らかにするための重要な結果であると考えられる。また、HMGB1の関与するシグナルは前立腺癌のみならず他臓器の腫瘍においても同様に存在すると考えられ、本研究で得られた知見は他のあらゆる癌腫へ応用可能である。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy2020
Author(s)
Xue Jiaming、Patergnani Simone、Giorgi Carlotta、Suarez Joelle、Goto Keisuke、Bononi Angela、Tanji Mika、Novelli Flavia、Pastorino Sandra、Xu Ronghui、Caroccia Natascia、Dogan A. Umran、Pass Harvey I.、Tognon Mauro、Pinton Paolo、Gaudino Giovanni、Mak Tak W.、Carbone Michele、Yang Haining
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 117
Issue: 41
Pages: 25543-25552
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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