Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model

Yes‐associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines...

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Autores principales: Hsu, Ping‐Chih, Miao, Jinbai, Huang, Zhen, Yang, Yi‐Lin, Xu, Zhidong, You, Joanna, Dai, Yuyuan, Yeh, Che‐Chung, Chan, Geraldine, Liu, Shu, Urisman, Anatoly, Yang, Cheng‐Ta, Jablons, David M., You, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
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Original Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980132/
https://www.ncbi.nlm.nih.gov/pubmed/29575527
http://dx.doi.org/10.1111/jcmm.13582
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author Hsu, Ping‐Chih
Miao, Jinbai
Huang, Zhen
Yang, Yi‐Lin
Xu, Zhidong
You, Joanna
Dai, Yuyuan
Yeh, Che‐Chung
Chan, Geraldine
Liu, Shu
Urisman, Anatoly
Yang, Cheng‐Ta
Jablons, David M.
You, Liang
author_facet Hsu, Ping‐Chih
Miao, Jinbai
Huang, Zhen
Yang, Yi‐Lin
Xu, Zhidong
You, Joanna
Dai, Yuyuan
Yeh, Che‐Chung
Chan, Geraldine
Liu, Shu
Urisman, Anatoly
Yang, Cheng‐Ta
Jablons, David M.
You, Liang
author_sort Hsu, Ping‐Chih
collection PubMed
description Yes‐associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030‐BrM3(K‐ras(G12C) mutation) and PC9‐BrM3 (EGFR (Δexon19) mutation) had a significantly decreased p‐YAP(S127)/YAP ratio compared to parental H2030 (K‐ras(G12C) mutation) and PC9 (EGFR (Δexon19) mutation) cells (P < .05). H2030‐BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030‐BrM3 cells (P < .05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030‐BrM3 cells (P < .05). We are first to show that mice inoculated with YAP shRNA‐transfected H2030‐BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P < .05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030‐BrM3 cell brain metastasis in a murine model.
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spelling pubmed-59801322018-06-07 Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model Hsu, Ping‐Chih Miao, Jinbai Huang, Zhen Yang, Yi‐Lin Xu, Zhidong You, Joanna Dai, Yuyuan Yeh, Che‐Chung Chan, Geraldine Liu, Shu Urisman, Anatoly Yang, Cheng‐Ta Jablons, David M. You, Liang J Cell Mol Med Original Articles Yes‐associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030‐BrM3(K‐ras(G12C) mutation) and PC9‐BrM3 (EGFR (Δexon19) mutation) had a significantly decreased p‐YAP(S127)/YAP ratio compared to parental H2030 (K‐ras(G12C) mutation) and PC9 (EGFR (Δexon19) mutation) cells (P < .05). H2030‐BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030‐BrM3 cells (P < .05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030‐BrM3 cells (P < .05). We are first to show that mice inoculated with YAP shRNA‐transfected H2030‐BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P < .05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030‐BrM3 cell brain metastasis in a murine model. John Wiley and Sons Inc. 2018-03-24 2018-06 /pmc/articles/PMC5980132/ /pubmed/29575527 http://dx.doi.org/10.1111/jcmm.13582 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Hsu, Ping‐Chih
Miao, Jinbai
Huang, Zhen
Yang, Yi‐Lin
Xu, Zhidong
You, Joanna
Dai, Yuyuan
Yeh, Che‐Chung
Chan, Geraldine
Liu, Shu
Urisman, Anatoly
Yang, Cheng‐Ta
Jablons, David M.
You, Liang
Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
title Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
title_full Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
title_fullStr Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
title_full_unstemmed Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
title_short Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
title_sort inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980132/
https://www.ncbi.nlm.nih.gov/pubmed/29575527
http://dx.doi.org/10.1111/jcmm.13582
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