DAL-1 attenuates epithelial-to mesenchymal transition in lung cancerReportar como inadecuado




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Journal of Experimental and Clinical Cancer Research

, 34:3

First Online: 22 January 2015Received: 12 October 2014Accepted: 22 December 2014DOI: 10.1186-s13046-014-0117-2

Cite this article as: Chen, X., Guan, X., Zhang, H. et al. J Exp Clin Cancer Res 2015 34: 3. doi:10.1186-s13046-014-0117-2

Abstract

BackgroundEpithelial-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.

MethodsThe 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.

ResultsDAL-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.

ConclusionsThese 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.

KeywordsDifferentially expressed in adenocarcinoma of the lung-1 Epithelial-mesenchymal transition Lung cancer E-cadherin HSPA5 AbbreviationsDAL-1Differentially expressed in adenocarcinoma of the lung-1

EMTEpithelial-to mesenchymal transition

NSCLCNon small cell carcinoma

HSPA5Heat shock protein A5

Xianliang Chen and Xiaoying Guan contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13046-014-0117-2 contains supplementary material, which is available to authorized users.

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Autor: Xianliang Chen - Xiaoying Guan - Huiyu Zhang - Xiaobin Xie - Hongyan Wang - Jie Long - Tonghui Cai - Shuhua Li - Zhen Liu

Fuente: https://link.springer.com/







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