Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties:importance of stem cell plasticity

• Material Type: 博士論文
• Title: Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties:importance of stem cell plasticity
• Author/Editor: 松元, 崇
• Author Heading: 松元, 崇
• Publication Date: 2018-03-20
• Publication Date (W3CDTF): 2018-03-20
• Alternative Title: ドキシサイクリンは癌幹細胞様特性のある細胞に選択的に小胞体ストレスを与えアポトーシスを誘導する : 癌幹細胞可塑性の重要性
• Contributor: 赤司, 浩一; 新井, 文用; 加藤, 聖子
• Degree grantor/type: 九州大学
• Date Granted: 2018-03-20
• Date Granted (W3CDTF): 2018-03-20
• Dissertation Number: 甲第13927号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第13927号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): Tumor heterogeneity can be traced back to a small subset of cancer stem cells (CSCs), which can be derived from a single stem cell and show chemoresistance. Recent studies showed that CSCs are sensitive to mitochondrial targeting antibiotics such as doxycycline. However, little is known about how cancer cells undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we show that under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents. Furthermore, those CSC-like properties could reversibly change depending on the culture conditions, suggesting some kinds of CSCs have plasticity in tumor microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed increased contact between mitochondria and mitochondrial associated-endoplasmic reticulum (ER) membranes (MAM). Mitochondrial targeting doxycycline induced activating transcription factor 4 (ATF4) mediated expression of ER stress response and led to p53-upregulated modulator of apoptosis (PUMA)-dependent apoptosis only in the cancer stem-like cells. We also found that doxycycline effectively suppressed the sphere formation in vitro and blocked CD44v9-expressing tumor growth in vivo. In summary, these data provide new molecular findings that monolayer cancer cells acquire CSC-like properties in a reversible manner. These findings provide important insights into CSC biology and a potential new treatment of targeting mitochondria dependency.; PubMed番号 : 29184058
• DOI: 10.15017/1931780; https://doi.org/10.15017/1931780
• Persistent ID (NDL): info:ndljp/pid/11122672; https://dl.ndl.go.jp/pid/11122672
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-08-03T23:36:01+09:00
• Date Created (W3CDTF): 2018-05-30
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://dx.doi.org/10.15017/1931780; http://hdl.handle.net/2324/1931780
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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