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

Ping Chih Hsu; Jinbai Miao; Zhen Huang; Yi Lin Yang; Zhidong Xu; Joanna You; Yuyuan Dai; Che Chung Yeh; Geraldine Chan; Shu Liu; Anatoly Urisman; Cheng Ta Yang; David M. Jablons; Liang You

doi:10.1111/jcmm.13582

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

Ping Chih Hsu
, Jinbai Miao
, Zhen Huang
, Yi Lin Yang
, Zhidong Xu
, Joanna You
, Yuyuan Dai
, Che Chung Yeh
, Geraldine Chan
, Shu Liu
, Anatoly Urisman
, Cheng Ta Yang
, David M. Jablons
, Liang You^*

^*此作品的通信作者

University of California at San Francisco
Chang Gung Memorial Hospital
Capital Medical University
Chinese Academy of Medical Sciences

研究成果: 期刊稿件 › 文章 › 同行評審

28 引文斯高帕斯（Scopus）

摘要

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.

原文	英語
頁（從 - 到）	3073-3085
頁數	13
期刊	Journal of Cellular and Molecular Medicine
卷	22
發行號	6
DOIs	https://doi.org/10.1111/jcmm.13582
出版狀態	已出版 - 06 2018
對外發佈	是

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© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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10.1111/jcmm.13582

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Hsu, P. C., Miao, J., Huang, Z., Yang, Y. L., Xu, Z., You, J., Dai, Y., Yeh, C. C., Chan, G., Liu, S., Urisman, A., Yang, C. T., Jablons, D. M., & You, L. (2018). Inhibition of yes-associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model. Journal of Cellular and Molecular Medicine, 22(6), 3073-3085. https://doi.org/10.1111/jcmm.13582

@article{a3e1b72a0bc649cab45009f37bf48e90,

title = "Inhibition of yes-associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model",

abstract = "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-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 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.",

keywords = "Hippo signalling, K-ras mutation, lung adenocarcinoma, metastasis, yes-associated protein",

author = "Hsu, \{Ping Chih\} and Jinbai Miao and Zhen Huang and Yang, \{Yi Lin\} and Zhidong Xu and Joanna You and Yuyuan Dai and Yeh, \{Che Chung\} and Geraldine Chan and Shu Liu and Anatoly Urisman and Yang, \{Cheng Ta\} and Jablons, \{David M.\} and Liang You",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley \& Sons Ltd and Foundation for Cellular and Molecular Medicine.",

year = "2018",

month = jun,

doi = "10.1111/jcmm.13582",

language = "英语",

volume = "22",

pages = "3073--3085",

journal = "Journal of Cellular and Molecular Medicine",

issn = "1582-1838",

publisher = "John Wiley and Sons Inc",

number = "6",

}

TY - JOUR

T1 - Inhibition of yes-associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model

AU - Hsu, Ping Chih

AU - Miao, Jinbai

AU - Huang, Zhen

AU - Yang, Yi Lin

AU - Xu, Zhidong

AU - You, Joanna

AU - Dai, Yuyuan

AU - Yeh, Che Chung

AU - Chan, Geraldine

AU - Liu, Shu

AU - Urisman, Anatoly

AU - Yang, Cheng Ta

AU - Jablons, David M.

AU - You, Liang

PY - 2018/6

Y1 - 2018/6

N2 - 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-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 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.

AB - 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-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 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.

KW - Hippo signalling

KW - K-ras mutation

KW - lung adenocarcinoma

KW - metastasis

KW - yes-associated protein

UR - https://www.scopus.com/pages/publications/85044282652

U2 - 10.1111/jcmm.13582

DO - 10.1111/jcmm.13582

M3 - 文章

C2 - 29575527

AN - SCOPUS:85044282652

SN - 1582-1838

VL - 22

SP - 3073

EP - 3085

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

IS - 6

ER -

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

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