FBI-1 inhibits epithelial-to-mesenchymal transition, migration, and invasion in lung adenocarcinoma A549 cells by downregulating transforming growth factor-beta 1 signaling pathway

Abstract

The factor binding inducer of short transcripts-1 (FBI-1) is a POZ-domain Kruppel-like (POK) family of transcription factors and is known as a protooncogene or tumor suppressor in various carcinomas. However, the role of FBI-1 on epithelial-to-mesenchymal transition (EMT) and invasiveness in lung cancer remains unknown. Preliminarily, clinical data such as tissue microarray, Kaplan-Meier, and Oncomine were analyzed to confirm the correlation between lung cancer metastasis and FBI-1. To investigate the function of FBI-1 in EMT in lung cancer, EMT was measured in FBI-1-deficient or FBI-1-overexpressing cells. FBI-1 showed decreased expression in tumors metastasized to lymph nodes than in the primary tumor. In addition, it was also associated with improved survival rates of lung cancer patients. FBI-1 knockdown improved E-to-N-cadherin switching, migration, and invasion in A549 cells, similar to the initiation of EMT stimulated by transforming growth factor- beta 1 (TGF-beta 1). In contrast, overexpression of FBI-1 inhibited the transcription and activation of Smad2, thereby interfering with EMT, despite stimulation by TGF-beta 1. These results suggest that FBI-1 plays a negative role in EMT in lung cancer via the TGF-beta 1 signaling pathway, implying its use as a new potential therapeutic target and diagnostic indicator for early stage of lung cancer metastasis.