Hypoxia Stimulates the Epithelial-to-Mesenchymal Transition in Lung Cancer Cells Through Accumulation of Nuclear β-Catenin

Abstract

Background/aim: Recent studies implied a significant role of hypoxia-inducible factor-1α (HIF1α) in cell transformation. This study aimed to assess the effects of HIF1α on the epithelial-to-mesenchymal transition (EMT) and tumorigenesis of lung adenocarcinoma cells.

Materials and methods: Invasion, migration and colony formation assays were used to evaluate cell transformation. Expression of EMT-related markers were analyzed by western blot, reverse-transcription polymerase chain reaction or zymography. A luciferase assay was carried out to access the transcriptional activity of β-catenin.

Results: Hypoxia enhanced migration, invasion and transformation of A549 lung adenocarcinoma cells. Hypoxic stimulation promoted the expression of EMT-related markers in lung cancer cells. The expression of HIF1α was found to be involved in hypoxia-mediated modulation of expression of snail family transcriptional repressors 1 (SNAI1) and 2 (SLUG). Hypoxia enhanced nuclear accumulation and transcriptional activity of β-catenin.

Conclusion: β-Catenin promotes expression of EMT-related genes and eventually contributes to the metastatic process.

Keywords: EMT; Lung cancer; epithelial–to–mesenchymal transition; hypoxia; β-catenin.