DAL-1/4.1B contributes to epithelial-mesenchymal transition via regulation of transforming growth factor-ß in lung cancer cell lines.

ABSTRACT

The present study aimed to investigate the effects of the tumor suppressor gene differentially expressed in adenocarcinoma of the lung 1 (DAL­1)/4.1B on early­stage adenocarcinoma of the lung. The role of DAL­1/4.1B in the epithelial­mesenchymal transition (EMT), which is implicated in cancer metastasis, was examined using DAL­1 knockdown and overexpression, followed by polymerase chain reaction and western blot analysis of EMT markers, as well as cell counting and cell migration/invasion assays. The results showed that DAL­1/4.1B has a role in transforming growth factor (TGF)­ß­induced EMT in non­small cell lung cancer cells. Silencing of DAL­1/4.1B with inhibitory RNAs altered the expression of numerous EMT markers, including E­cadherin and ß­catenin, whereas overexpression of DAL­1/4.1B had the opposite effect. In addition, DAL­1/4.1B expression was induced following TGF­ß treatment at the protein and mRNA level. DAL­1/4.1B deficiency impaired TGF­ß­induced EMT and increased cell migration and invasion. These results suggested that DAL­1/4.1B contributed to the EMT and may be important for tumor metastasis in lung cancer. Together with the results of a previous study by our group, the present study suggested that DAL­1/4.1B acts as a tumor suppressor in the early transformation process in lung cancer, while in later stages, it functions as an oncogene affecting the biological features of human lung carcinoma cells. The results of the present study provided evidence for the feasibility of utilizing DAL­1/4.1B as a target for lung cancer gene therapy.