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Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling
Breast cancer is the most common malignant disease occurring in women and represents a substantial proportion of the global cancer burden. In these patients, metastasis but not the primary tumor is the main cause of breast cancer-related deaths. Here, we report the novel finding that DN10764 (AZD776...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347771/ https://www.ncbi.nlm.nih.gov/pubmed/27829217 http://dx.doi.org/10.18632/oncotarget.13088 |
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author | Park, Joon-Suk Lee, ChuHee Kim, Hyun-Kyoung Kim, Dayea Son, Jung Beom Ko, Eunhwa Cho, Joong-Heui Kim, Nam-Doo Nan, Hong-Yan Kim, Choong-Yong Yoon, Sukkyoon Lee, Sun-Hwa Choi, Hwan Geun |
author_facet | Park, Joon-Suk Lee, ChuHee Kim, Hyun-Kyoung Kim, Dayea Son, Jung Beom Ko, Eunhwa Cho, Joong-Heui Kim, Nam-Doo Nan, Hong-Yan Kim, Choong-Yong Yoon, Sukkyoon Lee, Sun-Hwa Choi, Hwan Geun |
author_sort | Park, Joon-Suk |
collection | PubMed |
description | Breast cancer is the most common malignant disease occurring in women and represents a substantial proportion of the global cancer burden. In these patients, metastasis but not the primary tumor is the main cause of breast cancer-related deaths. Here, we report the novel finding that DN10764 (AZD7762, a selective inhibitor of checkpoint kinases 1 and 2) can suppress breast cancer metastasis. In breast cancer cells, DN10764 inhibited cell proliferation and GAS6-mediated AXL signaling, consequently resulting in suppressed migration and invasion. In addition, DN10764 induced caspase 3/7-mediated apoptosis in breast cancer cells and inhibited tube formation of human umbilical vein endothelial cells. Finally, DN10764 significantly suppressed the tumor growth and metastasis of breast cancer cells in in vivo metastasis models. Taken together, these data suggest that therapeutic strategies targeting AXL in combination with systemic therapies could improve responses to anti-cancer therapies and reduce breast cancer recurrence and metastases. |
format | Online Article Text |
id | pubmed-5347771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53477712017-03-31 Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling Park, Joon-Suk Lee, ChuHee Kim, Hyun-Kyoung Kim, Dayea Son, Jung Beom Ko, Eunhwa Cho, Joong-Heui Kim, Nam-Doo Nan, Hong-Yan Kim, Choong-Yong Yoon, Sukkyoon Lee, Sun-Hwa Choi, Hwan Geun Oncotarget Research Paper Breast cancer is the most common malignant disease occurring in women and represents a substantial proportion of the global cancer burden. In these patients, metastasis but not the primary tumor is the main cause of breast cancer-related deaths. Here, we report the novel finding that DN10764 (AZD7762, a selective inhibitor of checkpoint kinases 1 and 2) can suppress breast cancer metastasis. In breast cancer cells, DN10764 inhibited cell proliferation and GAS6-mediated AXL signaling, consequently resulting in suppressed migration and invasion. In addition, DN10764 induced caspase 3/7-mediated apoptosis in breast cancer cells and inhibited tube formation of human umbilical vein endothelial cells. Finally, DN10764 significantly suppressed the tumor growth and metastasis of breast cancer cells in in vivo metastasis models. Taken together, these data suggest that therapeutic strategies targeting AXL in combination with systemic therapies could improve responses to anti-cancer therapies and reduce breast cancer recurrence and metastases. Impact Journals LLC 2016-11-04 /pmc/articles/PMC5347771/ /pubmed/27829217 http://dx.doi.org/10.18632/oncotarget.13088 Text en Copyright: © 2016 Park et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Park, Joon-Suk Lee, ChuHee Kim, Hyun-Kyoung Kim, Dayea Son, Jung Beom Ko, Eunhwa Cho, Joong-Heui Kim, Nam-Doo Nan, Hong-Yan Kim, Choong-Yong Yoon, Sukkyoon Lee, Sun-Hwa Choi, Hwan Geun Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling |
title | Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling |
title_full | Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling |
title_fullStr | Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling |
title_full_unstemmed | Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling |
title_short | Suppression of the metastatic spread of breast cancer by DN10764 (AZD7762)-mediated inhibition of AXL signaling |
title_sort | suppression of the metastatic spread of breast cancer by dn10764 (azd7762)-mediated inhibition of axl signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347771/ https://www.ncbi.nlm.nih.gov/pubmed/27829217 http://dx.doi.org/10.18632/oncotarget.13088 |
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