TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin

Abstract

The Groucho transcriptional corepressor TLE1 protein has recently been shown to be a putative lung specific oncogene, but its underlying oncogenic activity in lung cancer has not been fully elucidated. In this report, we investigated whether TLE1 regulates lung cancer aggressiveness using the human lung adenocarcinoma cell line A549 as a model system. Through a combination of genetic approaches, we found that TLE1 potentiates Epithelial-to-Mesenchymal Transition (EMT) in A549 cells in part through suppression of the tumor suppressor gene E-cadherin. Exogenous expression of TLE1 in A549 cells resulted in heightened EMT phenotypes (enhanced fibroblastoid morphology and increased cell migratory potential) and in molecular alterations characteristic of EMT (downregulation of the epithelial marker E-cadherin and upregulation of the mesenchymal marker Vimentin). Conversely, downregulation of endogenous TLE1 expression in these cells resulted in reversal of basal EMT characterized by a cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Mechanistic studies showed that TLE1 suppresses E-cadherin expression at the transcriptional level in part by recruiting Histone Deacetylase (HDAC) activity to the E-cadherin promoter. Consistently, the HDAC inhibitor TSA partially reversed the TLE1-induced E-cadherin downregulation and cell migration, suggesting a role for HDACs in TLE1-mediated transcriptional repression of E-cadherin and EMT function. These findings uncover a novel role of TLE1 in regulating EMT in A549 cells through its repressive effect on E-cadherin and provide a mechanism for TLE1 oncogenic activity in lung cancer.

Lnc‐GIHCG promotes cell proliferation and migration in gastric cancer through miR‐ 1281 adsorption

“…Existing studies confirm that its abnormal expression may result in the occurrence and development of multiple tumors. For lung cancer, TLE1 participates in the progression of lung cancer by enhancing epithelial mesenchymal transition of lung cancer cells by inhibiting E‐cadherin expression (Yao et al, ). As shown by bioinformatic analysis, TLE1 was a potential target gene of miR‐1281 and miR‐1281 downregulated TLE1 expression.…”

The Anoikis Effector Bit1 Inhibits EMT through Attenuation of TLE1-Mediated Repression of E-Cadherin in Lung Cancer Cells

“…In both A549 and BEAS-2B parental lines, two Bit1 shRNA knockdown-positive clones and two control shRNA clones were pooled for further characterization. The control-GFP and GFP-TLE1 A549 pools of cells were generated by transduction with the lentiviral GFP-TLE1 or the empty control GFP construct (Open Biosystems, Huntsville, AL) [ 13 ].…”

“…The migratory ability of cells was quantified with the use of wound closure and Boyden chamber cell migration assays as described previously [ 13 ]. Wound closure experiments were performed by scarring cell monolayers with a sterile micropipette tip.…”

Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells

“…As described previously [27], HCC cells were fixed with 1% formaldehyde and processed with the ChIP-IT Enzymatic kit (Active Motif, Carlsbad, CA) following the manufacturer’s protocol. The resulting protein/DNA complexes were then immunoprecipitated overnight at 4°C using anti-SNAIL1 antibody(Abcam, MA, USA), non-specific IgG antibodies (Santa Cruz Biotechnology Inc., CA, USA), respectively, with protein G magnetic beads.…”