Open Access17‐ AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS 1/ YAP pathway
Author(s) -
Ye XiangYun,
Luo QingQuan,
Xu YunHua,
Tang NaiWang,
Niu XiaoMin,
Li ZiMing,
Shen ShengPing,
Lu Shun,
Chen ZhiWei
Publication year - 2015
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.12469
Subject(s) - apoptosis , cell growth , cancer research , cell cycle , biology , cell , oncogene , adenocarcinoma , chemistry , cancer , biochemistry , genetics
The large tumour suppressor 1 ( LATS 1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS 1 and the regulatory mechanisms of 17‐Allylamino‐17‐ demethoxygeldanamycin (17‐ AAG ) in lung adenocarcinoma ( LAC ). The aim of the present study was to investigate the correlation of LATS 1 and yes‐associated protein ( YAP ) expression with clinicopathological characteristics in LAC patients, and the effects of 17‐ AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS 1 was significantly lowered (26.7% versus 68.0%, P < 0.001), while that of YAP was elevated (76.0% versus 56.0%, P = 0.03) in LAC tissues compared to the adjacent non‐cancerous tissues; LAST 1 expression was negatively correlated with YAP expression ( r = 0.432, P < 0.001) and lymphatic invasion of the tumour ( P = 0.015). In addition, 17‐ AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E‐cadherin and p‐ LATS 1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17‐ AAG ‐treated groups than those in untreated group ( P < 0.01). Taken together, our findings indicate that decreased expression of LATS 1 is associated with lymphatic invasion of LAC , and 17‐ AAG suppresses growth and invasion of LAC cells via regulation of the LATS 1/ YAP pathway in vitro and in vivo , suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC .