Journal of Experimental & Clinical Cancer Research | |
DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer | |
Yajie Zhang1  Zhen Liu1  Shuhua Li1  Tonghui Cai1  Jie Long1  Hongyan Wang1  Xiaobin Xie1  Huiyu Zhang1  Xiaoying Guan1  Xianliang Chen1  | |
[1] Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, 195# Dongfeng West Road, Guangzhou 510180, Guangdong, People’s Republic of China | |
关键词: HSPA5; E-cadherin; Lung cancer; Epithelial-mesenchymal transition; Differentially expressed in adenocarcinoma of the lung-1; | |
Others : 1133648 DOI : 10.1186/s13046-014-0117-2 |
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received in 2014-10-12, accepted in 2014-12-22, 发布年份 2015 |
【 摘 要 】
Background
Epithelial-to mesenchymal transition (EMT) involves in metastasis, causing loss of epithelial polarity. Metastasis is the major cause of carcinoma-induced death, but mechanisms are poorly understood. Here we identify differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a protein belongs to the membrane-associated cytoskeleton protein 4.1 family, as an efficient suppressor of EMT in lung cancer.
Methods
The relationship between DAL-1 and EMT markers were analyzed by using immunohistochemistry in the clinical lung cancer tissues. Quantitative real-time PCR and western blot were used to characterize the expression of the EMT indicator mRNAs and proteins in DAL-1 overexpressed or knockdown cells. DAL-1 combined proteins were assessed by co-immunoprecipitation.
Results
DAL-1 levels were strongly reduced even lost in lymph node metastasis and advanced pathological stage of human lung carcinomas. Overexpression of DAL-1 altered the expression of numerous EMT markers, such as E-cadherin, β-catenin Vimentin and N-cadherin expression, meanwhile changed the morphological shape of lung cancer cells, and whereas silencing DAL-1 had an opposite effect. DAL-1 directly combined with E-cadherin promoter and regulated its expression that could be the reason for impairing EMT and decreasing cell migration and invasion. Strikingly, HSPA5 was found as DAL-1 direct binding protein.
Conclusions
These results suggest that tumor suppressor DAL-1 could also attenuate EMT and be important for tumor metastasis in the early transformation process in lung cancer.
【 授权许可】
2015 Chen et al.; licensee BioMed Central.
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