Elucidating the mechanism for induction of senescence-associated secretory phenotype by Epstein-Barr virus
| Project/Area Number |
17H04343
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉崎 智一 金沢大学, 医学系, 教授 (70262582)
近藤 悟 金沢大学, 附属病院, 講師 (70436822)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | 細胞老化 / Epstein-Barrウイルス / ヒト乳頭腫ウイルス / ミトコンドリア / 転移 / HPV / EBV / ROS / SOD2 / シチジンデアミナーゼ / 活性酸素種 / 癌関連線維芽細胞 / Epstein-Barr ウイルス / 細胞老化関連分泌形質 / 上咽頭癌 / 癌幹細胞ニッチ |
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| Outline of Final Research Achievements |
In the current study, we cannot find any correlated biological background between senescence-associated secretory phenotype (SASP), and cancerization and metastatic potential in both nasopharyngeal carcinoma (NPC) and oropharyngeal carcinoma (OPC). In both carcinomas, especially in NPC, mitochondrial DNA mutations were strongly correlated with metastatic potential of NPCs. We found many mitochondrial DNA mutations were due to the effect ofcytidine deaminases (CDAs) in NPC. On the other hands, the mutations were caused both by CDAs and reactive oxigen species in OPCs.
For the above-mentioned result, the existence of the phenomenon that metastasis was promoted by the mutatiions of the mitochondrial DNA was suggested. And an elucidation of the mechanisms to relate metastasis to mitochondrial DNA mutations is needed in the future study.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は当初、SASPと発癌・転移の関連性を解明すべく開始したが、その関連性は証明されなかった。SASPの誘因としてミトコンドリアDNAの変異が指摘されているが、本研究では、次世代シークエンサーによる解析の結果、SASP現象よりもミトコンドリアDNAの変異が転移促進の主要因の一つとして抽出された。
頭頸部癌、特にウイルス関連癌の転移機構研究の方向性として、ミトコンドリアDNA変異による転移機構の解明が今後の研究課題として示された意義は大きい。
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Report
(5 results)
Research Products
(42 results)
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[Journal Article] EBV-LMP1 induces APOBEC3s and mitochondrial DNA hypermutation in nasopharyngeal cancer2020
Author(s)
Wakae K, Kondo S, Pham HT, Wakisaka N, Que L, Li Y, Zheng X, Fukano K, Kitamura K, Watashi K, Aizaki H, Ueno T, Moriyama-Kita M, Ishikawa K, Nakanishi Y, Endo K, Muramatsu M, Yoshizaki T.
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Journal Title
Cancer Med
Volume: 20
Issue: 20
Pages: 7663-7671
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overexpression of Semaphorin 3A is a Marker Associated with Poor Prognosis in Patients with Nasopharyngeal Carcinoma.2019
Author(s)
Imoto T, Kondo S, Wakisaka N, Hai PT, Seishima N, Kano M, Ueno T, Mizokami H, Nakanishi Y, Hatano M, Endo K, Sugimoto H, Moriyama-Kita M, Yoshizaki T.
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Journal Title
Microorganisms
Volume: 17
Issue: 3
Pages: 423-423
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Third Epidemiological Analysis of Nasopharyngeal Carcinoma in the Central Region of Japan from 2006 to 20152019
Author(s)
Kanno M, Narita N, Fujimoto Y, Wakisaka N, Yoshizaki T, Kodaira T, Makita C, Sato Y, Yamazaki K, Wakaoka T, Shimode Y, Tsuji H, Kito R, Ishinaga H, Hosokawa S, Takakura H, Nishimura K, Matoba T, Fujieda S.
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Journal Title
Cancers
Volume: 11
Issue: 8
Pages: 1180-1180
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Modulation of Tumor Microenvironment by Epstein-Barr virus Latent Membrane Protein-1 in Nasopharyngeal Carcinoma2018
Author(s)
Yoshizaki T, Kondo S, Endo K, Nakanishi Y, Aga M, Kobayashi E, Hirai N, Sugimoto H, Hatano M, Ueno T, Ishikawa K, Wakisaka N
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Journal Title
Cancer Sci
Volume: 109
Issue: 2
Pages: 272-278
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression of interferon regulatory factor 7 correlates with the expression of Epstein-Barr Virus latent membrane protein 1 and cervical lymph node metastasis in nasopharyngeal cancer2017
Author(s)
Kondo S, Endo K, Wakisaka N, Aga M, Kano M, Seishima N, Imoto T, Kobayashi E, Moriyama-Kita M, Nakanishi Y, Murono S, Pagano JS, Yoshizaki T
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Journal Title
Pathology International
Volume: 67
Issue: 9
Pages: 461-466
DOI
Related Report
Peer Reviewed
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[Journal Article] Usefulness of human papillomavirus detection in oral rinse as a biomarker of oropharyngeal cancer2017
Author(s)
Yoshida H, Murono S, Ueno T, Nakanishi Y, Tsuji A, Hatano M, Endo K, Kondo S, Sugimoto H, Wakisaka N, Yoshizaki T
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Journal Title
Acta Otolaryngol
Volume: -
Issue: 7
Pages: 773-777
DOI
Related Report
Peer Reviewed
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[Journal Article] EBV infection is prevalent in the adenoid and palatine tonsils in adults2017
Author(s)
Seishima N, Kondo S, Wakisaka N, Kobayashi E, Imoto T, Moriyama-Kita M, Nakanishi Y, Endo K, Murono S, Sugimoto H, Hatano M, Ueno T, Yoshizaki T.
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Journal Title
J Med Virol
Volume: 89
Issue: 6
Pages: 1088-1095
DOI
Related Report
Peer Reviewed
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[Presentation] Detection of Sentinel Node using contrast-enhanced agent, SonazoidTM, and evaluation of its metastasis with Superb Microvascular Imaging (SMI) in oral and oropharyngeal cancers: A preliminary study2018
Author(s)
Wakisaka N, Endo K, Kitazawa T, Shimode Y, Kato K,Moriyama-Kita M, Koda W, Ikeda H, Ishikawa K, Nakanishi Y, Kondo S, Sugimoto H, Yoshimura K, Tsuji H, Kawashiri S, Omoto K, Hasegawa H, Yoshizaki T
Organizer
International Sentinel Node Society Biennual Meeting 2018
Related Report
Int'l Joint Research
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