17‐AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Ye, Xiang‐Yun; Luo, Qing‐Quan; Xu, Yun‐Hua; Tang, Nai‐Wang; Niu, Xiao‐Min; Li, Zi‐Ming; Shen, Sheng‐Ping; Lu, Shun; Chen, Zhi‐Wei
• Is Part Of: Journal of cellular and molecular medicine. Volume 19:Issue 3(2015)
• Page Start: 651
• Page End: 663
• Publication Date: 2015-03
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12469
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12469-abs-0001"> <title>Abstract</title> <p>The large tumour suppressor 1 (LATS1) 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 LATS1 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 LATS1 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 LATS1 was significantly lowered (26.7% <italic>versus</italic> 68.0%, <italic>P</italic> < 0.001), while that of YAP was elevated (76.0% <italic>versus</italic> 56.0%, <italic>P</italic> = 0.03) in LAC tissues compared to the adjacent non‐cancerous tissues; LAST1 expression was negatively correlated with YAP expression (<italic>r</italic> = 0.432, <italic>P</italic> < 0.001) and lymphatic invasion of the tumour (<italic>P</italic> = 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‐LATS1, 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 (<italic>P</italic> < 0.01). Taken together, our findings indicate that decreased expression of LATS1 is associated with lymphatic invasion of LAC, and 17‐AAG suppresses growth and invasion of LAC cells <italic>via</italic> regulation of the LATS1/YAP pathway <italic>in vitro</italic> and <italic>in vivo</italic>, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC.</p> </abstract>