期刊
THORACIC CANCER
卷 10, 期 4, 页码 848-855出版社
WILEY
DOI: 10.1111/1759-7714.13013
关键词
Epithelial-mesenchymal transition (EMT); ING5; lung cancer; phosphorylation; WNT; -catenin
资金
- National Natural Science Foundation of China [81672269]
- Natural Science Foundation of Shaanxi Province [2017JM8034]
- No. 309 Hospital of PLA [2016MS-016]
BackgroundING5 is the last member of the Inhibitor of Growth (ING) candidate tumor suppressor family that has been implicated in multiple cellular functions, including cell cycle regulation, apoptosis, and chromatin remodeling. Our previous study showed that ING5 overexpression inhibits lung cancer aggressiveness and epithelial-mesenchymal transition (EMT), with unknown mechanisms. MethodsWestern blotting was used to detect total and phosphorylated levels of -catenin and EMT-related proteins. Immunofluorescent staining was used to observe E-cadherin expression. Proliferation and colony formation, wound healing, and Transwell migration and invasion assays were performed to study the proliferative and invasive abilities of cancer cells. ResultsING5 overexpression promotes phosphorylation of -catenin at Ser33/37, leading to a decreased -catenin protein level. Small hairpin RNA-mediated ING5 knockdown significantly increased the -catenin level and inhibited phosphorylation of -catenin S33/37. Treatment with the WNT/-catenin inhibitor XAV939 inhibited ING5-knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of -catenin S33/37 and a decreased -catenin level. XAV939 also impaired ING5-knockdown-induced EMT, as indicated by upregulated expression of the EMT marker E-cadherin, an epithelial marker; and decreased expression of N-cadherin, a mesenchymal marker, and EMT-related transcription factors, including Snail, Slug, Twist, and Smad3. Furthermore, XAV939 could inhibit the activation of both IL-6/STAT3 and PI3K/Akt signaling pathways. ConclusionING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/-catenin pathway.
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