Ligand independent aryl hydrocarbon receptor inhibits lung cancer cell invasion by degradation of Smad4
Journal
Cancer Letters
Journal Volume
376
Journal Issue
2
Pages
211-217
Date Issued
2016
Author(s)
JAW-JOU KANG
Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Although AhR plays a crucial role in air toxicant-induced carcinogenesis, AhR expression was shown to negatively regulate tumorigenesis. Therefore, in the present study, we investigated the effect of AhR without ligand treatment on cancer invasion in lung cancer cell lines. Lung cancer cells expressing lower levels of AhR showed higher invasion ability (H1299 cells) compared with cells expressing higher levels of AhR (A549 cells). Overexpression of AhR in H1299 cells inhibited the invasion ability. We found that vimentin expression was inhibited in AhR-overexpressing H1299 cells. Additionally, the expression of EMT-related transcriptional factors Snail and ID-1 decreased. Interestingly, we found that Smad4 degradation was induced in AhR-overexpressing H1299 cells. Our data showed that AhR could interact with Jun-activation domain binding protein (Jab1) and Smad4, which may cause degradation of Smad4 by the proteasome. Our data suggest that AhR affects the transforming growth factor-β signaling pathway by inducing Smad4 degradation by the proteasome and suppressing tumor metastasis via epithelial to mesenchymal transition reduction in lung cancer cells. ? 2016.
Subjects
Aryl hydrocarbon receptor; Epithelial to mesenchymal transition; Jun-activation domain binding protein; Lung cancer; Smad4; Transforming growth factor-β
SDGs
Other Subjects
aromatic hydrocarbon receptor; cell protein; inhibitor of differentiation 1; Jun activation domain binding protein 1; proteasome; Smad4 protein; transcription factor Snail; transforming growth factor beta; unclassified drug; vimentin; AHR protein, human; aromatic hydrocarbon receptor; basic helix loop helix transcription factor; COPS5 protein, human; ID1 protein, human; inhibitor of differentiation 1; ligand; peptide hydrolase; proteasome; signal peptide; Smad4 protein; SMAD4 protein, human; transcription factor Snail; vimentin; A549 cell line; Article; cancer cell line; cancer inhibition; cell specificity; controlled study; epithelial mesenchymal transition; H1299 cell line; human; human cell; lung cancer; metastasis inhibition; priority journal; protein analysis; protein degradation; protein expression; protein function; protein protein interaction; signal transduction; tumor invasion; adenocarcinoma; cell motion; gene expression regulation; genetic transfection; genetics; lung tumor; metabolism; non small cell lung cancer; pathology; phenotype; protein degradation; RNA interference; tumor cell line; tumor invasion; ubiquitination; Adenocarcinoma; Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Differentiation Protein 1; Intracellular Signaling Peptides and Proteins; Ligands; Lung Neoplasms; Neoplasm Invasiveness; Peptide Hydrolases; Phenotype; Proteasome Endopeptidase Complex; Proteolysis; Receptors, Aryl Hydrocarbon; RNA Interference; Signal Transduction; Smad4 Protein; Snail Family Transcription Factors; Transfection; Ubiquitination; Vimentin
Type
journal article