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LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promi...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614583/ https://www.ncbi.nlm.nih.gov/pubmed/28955993 http://dx.doi.org/10.1016/j.bbrep.2016.11.015 |
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author | Jotatsu, Takanobu Yagishita, Shigehiro Tajima, Ken Takahashi, Fumiyuki Mogushi, Kaoru Hidayat, Moulid Wirawan, Aditya Ko, Ryo Kanemaru, Ryota Shimada, Naoko Mitani, Keiko Saito, Tsuyoshi Takamochi, Kazuya Suzuki, Kenji Kohsaka, Shinji Kojima, Shinya Mukae, Hiroshi Yatera, Kazuhiro Takahashi, Kazuhisa |
author_facet | Jotatsu, Takanobu Yagishita, Shigehiro Tajima, Ken Takahashi, Fumiyuki Mogushi, Kaoru Hidayat, Moulid Wirawan, Aditya Ko, Ryo Kanemaru, Ryota Shimada, Naoko Mitani, Keiko Saito, Tsuyoshi Takamochi, Kazuya Suzuki, Kenji Kohsaka, Shinji Kojima, Shinya Mukae, Hiroshi Yatera, Kazuhiro Takahashi, Kazuhisa |
author_sort | Jotatsu, Takanobu |
collection | PubMed |
description | Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promising agents targeting genetic alterations that were already under investigation, results have been disappointing. Achievements in targeted therapeutics have not been observed for over 30 years. Therefore, the underlying disease biology and novel targets urgently require a better understanding. Epigenetic regulation is deeply involved in the cellular plasticity that could shift tumor cells to the malignant phenotype. We have focused on a histone modifier, LSD1, that is overexpressed in SCLC and is a potent therapeutic target. Interestingly, the LSD1 splice variant LSD1+8a, the expression of which has been reported to be restricted to neural tissue, was detected and was involved in the expression of neuroendocrine marker genes in SCLC cell lines. Cells with high expression of LSD1+8a were resistant to CDDP and LSD1 inhibitor. Moreover, suppression of LSD1+8a inhibited cell proliferation, indicating that LSD1+8a could play a critical role in SCLC. These findings suggest that LSD1+8a should be considered a novel therapeutic target in SCLC. |
format | Online Article Text |
id | pubmed-5614583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56145832017-09-27 LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer Jotatsu, Takanobu Yagishita, Shigehiro Tajima, Ken Takahashi, Fumiyuki Mogushi, Kaoru Hidayat, Moulid Wirawan, Aditya Ko, Ryo Kanemaru, Ryota Shimada, Naoko Mitani, Keiko Saito, Tsuyoshi Takamochi, Kazuya Suzuki, Kenji Kohsaka, Shinji Kojima, Shinya Mukae, Hiroshi Yatera, Kazuhiro Takahashi, Kazuhisa Biochem Biophys Rep Research Article Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promising agents targeting genetic alterations that were already under investigation, results have been disappointing. Achievements in targeted therapeutics have not been observed for over 30 years. Therefore, the underlying disease biology and novel targets urgently require a better understanding. Epigenetic regulation is deeply involved in the cellular plasticity that could shift tumor cells to the malignant phenotype. We have focused on a histone modifier, LSD1, that is overexpressed in SCLC and is a potent therapeutic target. Interestingly, the LSD1 splice variant LSD1+8a, the expression of which has been reported to be restricted to neural tissue, was detected and was involved in the expression of neuroendocrine marker genes in SCLC cell lines. Cells with high expression of LSD1+8a were resistant to CDDP and LSD1 inhibitor. Moreover, suppression of LSD1+8a inhibited cell proliferation, indicating that LSD1+8a could play a critical role in SCLC. These findings suggest that LSD1+8a should be considered a novel therapeutic target in SCLC. Elsevier 2016-12-01 /pmc/articles/PMC5614583/ /pubmed/28955993 http://dx.doi.org/10.1016/j.bbrep.2016.11.015 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Jotatsu, Takanobu Yagishita, Shigehiro Tajima, Ken Takahashi, Fumiyuki Mogushi, Kaoru Hidayat, Moulid Wirawan, Aditya Ko, Ryo Kanemaru, Ryota Shimada, Naoko Mitani, Keiko Saito, Tsuyoshi Takamochi, Kazuya Suzuki, Kenji Kohsaka, Shinji Kojima, Shinya Mukae, Hiroshi Yatera, Kazuhiro Takahashi, Kazuhisa LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer |
title | LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer |
title_full | LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer |
title_fullStr | LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer |
title_full_unstemmed | LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer |
title_short | LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer |
title_sort | lsd1/kdm1 isoform lsd1+8a contributes to neural differentiation in small cell lung cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614583/ https://www.ncbi.nlm.nih.gov/pubmed/28955993 http://dx.doi.org/10.1016/j.bbrep.2016.11.015 |
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