Abstract
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% 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; LAST1 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-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 (P < 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 via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC.
Highlights
Heat shock proteins (HSPs) are highly conserved proteins and their expression is dependent on the level of various cellular stresses
The decreased expression of large tumour suppressor 1 (LATS1) is inversely correlated with lymph node metastasis in gastric cancer, and one of the reasons for loss of LATS1 expression lies in the hypermethylation of LATS1 in the promoter regions [24]
Few studies show that LATS1 is overexpressed in cervical cancers and basal-like breast cancers [26], and the LATS1 methylation statuses do not correlate with survival of lung cancer patients [27]
Summary
Heat shock proteins (HSPs) are highly conserved proteins and their expression is dependent on the level of various cellular stresses. Their function is essential for normal cell viability and growth. HSP90 interacts with proteins mediating cell signalling involved in essential processes such as proliferation, cell cycle control, angiogenesis and. A promising activity is reported regarding 17-AAG in HER2-positive breast cancer and ALK-mutated lung cancers [5]. 17-AAG induces the down-regulation of critical HSP90 protein clients and results in cell cycle arrest and cell apoptosis in urinary bladder cancer cells [6]. Blockade of HSP90 by 17AAG antagonizes murine double minute X and synergizes with Nutlin to induce a 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
