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

被引：30
|
作者：
Liu, Kao-Hui [1 ,2 ]
Tsai, Yi-Ta [2 ]
Chin, Szu-Ying [1 ]
Lee, Woan-Ruoh [1 ,2 ,3 ]
Chen, Yen-Chou [2 ,4 ,5 ,6 ]
Shen, Shing-Chuan [2 ,3 ,4 ]
机构：
[1] Taipei Med Univ, Dept Dermatol, Shuang Ho Hosp, New Taipei, Taiwan
[2] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan
[3] Taipei Med Univ, Coll Med, Sch Med, Dept Dermatol, Taipei, Taiwan
[4] Taipei Med Univ, Coll Med, PhD Program Med, Taipei, Taiwan
[5] Taipei Med Univ Hosp, Canc Res Ctr, Taipei, Taiwan
[6] Taipei Med Univ Hosp, Orthoped Res Ctr, Taipei, Taiwan
来源：
ANTICANCER RESEARCH | 2018年 / 38卷 / 11期
关键词：
Lung cancer; hypoxia; epithelial-to-mesenchymal transition; EMT; beta-catenin; E-CADHERIN EXPRESSION; MATRIX METALLOPROTEINASES; UP-REGULATION; SLUG; EMT; TRANSCRIPTION; METASTASIS; REPRESSION; INHIBITOR; MIGRATION;
D O I：
10.21873/anticanres.12986
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background/Aim: Recent studies implied a significant role of hypoxia-inducible factor-1 alpha (HIF1 alpha) in cell transformation. This study aimed to assess the effects of HIF1 alpha 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 beta-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 HIF1 alpha was found to be involved in hypoxia-mediated modulation of expression of snail family transcriptional repressors 1(SNA11) and 2(SLUG). Hypoxia enhanced nuclear accumulation and transcriptional activity of beta-catenin. Conclusion: beta-Catenin promotes expression of EMT-related genes and eventually contributes to the metastatic process.
引用
收藏
页码：6299 / 6308
页数：10
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