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

Research paper by Kao-Hui KH Liu, Yi-Ta YT Tsai, Szu-Ying SY Chin, Woan-Ruoh WR Lee, Yen-Chou YC Chen, Shing-Chuan SC Shen

Indexed on: 07 Nov '18Published on: 07 Nov '18Published in: Anticancer research



Abstract

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. 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. 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. β-Catenin promotes expression of EMT-related genes and eventually contributes to the metastatic process. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.