Open AccessInhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model
Author(s) -
Hsu PingChih,
Miao Jinbai,
Huang Zhen,
Yang YiLin,
Xu Zhidong,
You Joanna,
Dai Yuyuan,
Yeh CheChung,
Chan Geraldine,
Liu Shu,
Urisman Anatoly,
Yang ChengTa,
Jablons David M.,
You Liang
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13582
Subject(s) - ctgf , cancer research , metastasis , biology , rna , transfection , messenger rna , adenocarcinoma , small interfering rna , microbiology and biotechnology , small hairpin rna , hippo signaling pathway , brain metastasis , cell culture , gene , cancer , growth factor , receptor , genetics
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 PC 9‐BrM3 ( EGFR Δexon19 mutation) had a significantly decreased p‐ YAP (S127)/ YAP ratio compared to parental H2030 (K‐ras G12C mutation) and PC 9 ( EGFR Δexon19 mutation) cells ( P < .05). H2030‐BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR 61 compared to parental H2030 cells ( P < .05). Inhibition of YAP by short hairpin RNA (sh RNA ) and small interfering RNA (si RNA ) significantly decreased mRNA expression in downstream genes CTGF and CYR 61 in H2030‐BrM3 cells ( P < .05). In addition, inhibiting YAP by YAP sh RNA significantly decreased migration and invasion abilities of H2030‐BrM3 cells ( P < .05). We are first to show that mice inoculated with YAP sh RNA ‐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 sh RNA suppresses H2030‐BrM3 cell brain metastasis in a murine model.