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Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo
BACKGROUND: Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS: The expression of YAP in CM...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012077/ https://www.ncbi.nlm.nih.gov/pubmed/27599610 http://dx.doi.org/10.1186/s13046-016-0414-z |
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author | Li, Hui Huang, Zhenglan Gao, Miao Huang, Ningshu Luo, Zhenhong Shen, Huawei Wang, Xin Wang, Teng Hu, Jing Feng, Wenli |
author_facet | Li, Hui Huang, Zhenglan Gao, Miao Huang, Ningshu Luo, Zhenhong Shen, Huawei Wang, Xin Wang, Teng Hu, Jing Feng, Wenli |
author_sort | Li, Hui |
collection | PubMed |
description | BACKGROUND: Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS: The expression of YAP in CML cells was determined by western blotting. Next, the effects of YAP knockdown and YAP inhibitor on CML cells were evaluated by MTT assay, flow cytometry (FCM) and Wright’s staining. Moreover, K562 induced mice model was employed to further investigate the role of YAP in vivo. RESULTS: YAP was overexpressed in CML cells. Knockdown of YAP by si-RNA or inhibition the function of YAP using verteporfin (VP) not only inhibited the proliferation, induced the apoptosis of CML cells but also reduced the expression of YAP target genes c-myc and survivin. Additionally, VP enhanced the efficacy of imatinib (IM) in vitro and suppressed leukemogenesis in vivo. CONCLUSION: Our results indicate that YAP may play an important role in the proliferation and leukemogenesis of CML cells. Genetic or pharmacological inhibition of YAP provides a novel treatment strategy for CML. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0414-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5012077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50120772016-09-07 Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo Li, Hui Huang, Zhenglan Gao, Miao Huang, Ningshu Luo, Zhenhong Shen, Huawei Wang, Xin Wang, Teng Hu, Jing Feng, Wenli J Exp Clin Cancer Res Research BACKGROUND: Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS: The expression of YAP in CML cells was determined by western blotting. Next, the effects of YAP knockdown and YAP inhibitor on CML cells were evaluated by MTT assay, flow cytometry (FCM) and Wright’s staining. Moreover, K562 induced mice model was employed to further investigate the role of YAP in vivo. RESULTS: YAP was overexpressed in CML cells. Knockdown of YAP by si-RNA or inhibition the function of YAP using verteporfin (VP) not only inhibited the proliferation, induced the apoptosis of CML cells but also reduced the expression of YAP target genes c-myc and survivin. Additionally, VP enhanced the efficacy of imatinib (IM) in vitro and suppressed leukemogenesis in vivo. CONCLUSION: Our results indicate that YAP may play an important role in the proliferation and leukemogenesis of CML cells. Genetic or pharmacological inhibition of YAP provides a novel treatment strategy for CML. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0414-z) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-06 /pmc/articles/PMC5012077/ /pubmed/27599610 http://dx.doi.org/10.1186/s13046-016-0414-z Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Li, Hui Huang, Zhenglan Gao, Miao Huang, Ningshu Luo, Zhenhong Shen, Huawei Wang, Xin Wang, Teng Hu, Jing Feng, Wenli Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
title | Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
title_full | Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
title_fullStr | Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
title_full_unstemmed | Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
title_short | Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
title_sort | inhibition of yap suppresses cml cell proliferation and enhances efficacy of imatinib in vitro and in vivo |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012077/ https://www.ncbi.nlm.nih.gov/pubmed/27599610 http://dx.doi.org/10.1186/s13046-016-0414-z |
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