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Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells
https://repo.qst.go.jp/records/77677
https://repo.qst.go.jp/records/7767797d5f009-91f5-48ea-a2db-3a9493fafe25
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-11-28 | |||||
| タイトル | ||||||
| タイトル | Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Ho Kim, Eun
× Ho Kim, Eun× Jo, Yunhui× Sai, Sei× Mung-Jin, Park× Jeong-Yub, Kim× Su Kim, Jin× Yeon-Joo, Lee× Jae-Min, Cho× Seo-Young, Kwak× Jeong-Hwa, Baek× Kyoung Jeong, Youn× Jie-Young, Song× Yoon, Myonggeun× Sang-Gu, Hwang× Ho Kim, Eun× Sei, Sai |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Tumor-treating fields (TTFs) - a type of electromagnetic field-based therapy using low-intensity electrical fields - has recently been characterized as a potential anticancer therapy for glioblastoma multiforme (GBM). However, the molecular mechanisms involved remain poorly understood. Our results show that the activation of autophagy contributes to the TTF-induced anti-GBM activity in vitro or in vivo and GBM patient stem cells or primary in vivo culture systems. TTF-treatment upregulated several autophagy-related genes (~2-fold) and induced cytomorphological changes. TTF-induced autophagy in GBM was associated with decreased Akt2 expression, not Akt1 or Akt3, via the mTOR/p70S6K pathway. An Affymetrix GeneChip miRNA 4.0 Array analysis revealed that TTFs altered the expression of many microRNAs (miRNAs). TTF-induced autophagy upregulated miR-29b, which subsequently suppressed the Akt signaling pathway. A luciferase reporter assay confirmed that TTFs induced miR-29b to target Akt2, negatively affecting Akt2 expression thereby triggering autophagy. TTF-induced autophagy suppressed tumor growth in GBM mouse models subjected to TTFs as determined by positron emission tomography and computed tomography (PET-CT). GBM patient stem cells and a primary in vivo culture system with high Akt2 levels also showed TTF-induced inhibition. Taken together, our results identified autophagy as a critical cell death pathway triggered by TTFs in GBM and indicate that TTF is a potential treatment option for GBM. | |||||
| 書誌情報 |
Oncogene 巻 38, 号 39, p. 6630-6646, 発行日 2019-01 |
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| 出版者 | ||||||
| 出版者 | Nature Publishing Group | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0950-9232 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 31375748 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41388-019-0882-7 | |||||
