دورية أكاديمية
Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells
| العنوان: | Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells |
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| المؤلفون: | Chiaki Fujiwara, Yukiko Muramatsu, Megumi Nishii, Kazuhiro Tokunaka, Hidetoshi Tahara, Masaru Ueno, Takao Yamori, Yoshikazu Sugimoto, Hiroyuki Seimiya |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Telomerase Inhibition, Telomerase Activity, Acute Deleterious Effects, Telomere Shortening, Hutchinson-Gilford Progeria Syndrome (HGPS), Medicine, Science |
| الوصف: | Abstract Telomere maintenance by telomerase activity supports the infinite growth of cancer cells. MST-312, a synthetic telomerase inhibitor, gradually shortens telomeres at non-acute lethal doses and eventually induces senescence and apoptosis of telomerase-positive cancer cells. Here we report that MST-312 at higher doses works as a dual inhibitor of telomerase and DNA topoisomerase II and exhibits acute anti-proliferative effects on cancer cells and xenografted tumours in vivo. Our cell-based chemical fingerprinting approach revealed that cancer cells with shorter telomeres and lower expression of lamin A, a nuclear architectural protein, exhibited higher sensitivity to the acute deleterious effects of MST-312, accompanied by formation of telomere dysfunction-induced foci and DNA double-strand breaks. Telomere elongation and lamin A overexpression attenuated telomeric and non-telomeric DNA damage, respectively, and both conferred resistance to apoptosis induced by MST-312 and other DNA damaging anticancer agents. These observations suggest that sufficient pools of telomeres and a nuclear lamina component contribute to the cellular robustness against DNA damage induced by therapeutic treatment in human cancer cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-018-33139-x |
| URL الوصول: | https://doaj.org/article/bcff0d57a37a40e7bac59241a17f8c5f |
| رقم الأكسشن: | edsdoj.bcff0d57a37a40e7bac59241a17f8c5f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-018-33139-x |