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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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.
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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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