ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway
Background ING5 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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-04-01
|
| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.13013 |
| _version_ | 1797845494469230592 |
|---|---|
| author | Xin‐Li Liu Jin Meng Xu‐Tao Zhang Xiao‐Hua Liang Feng Zhang Guan‐Ren Zhao Tao Zhang |
| author_facet | Xin‐Li Liu Jin Meng Xu‐Tao Zhang Xiao‐Hua Liang Feng Zhang Guan‐Ren Zhao Tao Zhang |
| author_sort | Xin‐Li Liu |
| collection | DOAJ |
| description | Background ING5 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. Methods Western blotting was used to detect total and phosphorylated levels of β‐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. Results ING5 overexpression promotes phosphorylation of β‐catenin at Ser33/37, leading to a decreased β‐catenin protein level. Small hairpin RNA‐mediated ING5 knockdown significantly increased the β‐catenin level and inhibited phosphorylation of β‐catenin S33/37. Treatment with the WNT/β‐catenin inhibitor XAV939 inhibited ING5‐knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of β‐catenin S33/37 and a decreased β‐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. Conclusion ING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/β‐catenin pathway. |
| first_indexed | 2024-04-09T17:39:57Z |
| format | Article |
| id | doaj.art-bd5d814bbe534d66b6ad96a37c59edc8 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-04-09T17:39:57Z |
| publishDate | 2019-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-bd5d814bbe534d66b6ad96a37c59edc82023-04-17T06:34:28ZengWileyThoracic Cancer1759-77061759-77142019-04-0110484885510.1111/1759-7714.13013ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathwayXin‐Li Liu0Jin Meng1Xu‐Tao Zhang2Xiao‐Hua Liang3Feng Zhang4Guan‐Ren Zhao5Tao Zhang6Department of Thoracic Surgery, Tangdu Hospital Fourth Military Medical University Xi'an ChinaDepartment of Pharmacology, School of Pharmacy Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine Fourth Military Medical University Xi'an ChinaDepartment of Pharmacology, School of Pharmacy Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine Fourth Military Medical University Xi'an ChinaDepartment of Thoracic Surgery, Tangdu Hospital Fourth Military Medical University Xi'an ChinaDepartment of Pharmacology, School of Pharmacy Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine Fourth Military Medical University Xi'an ChinaDepartment of Pharmacy PLA No. 309 Hospital Beijing ChinaDepartment of Thoracic Surgery, Tangdu Hospital Fourth Military Medical University Xi'an ChinaBackground ING5 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. Methods Western blotting was used to detect total and phosphorylated levels of β‐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. Results ING5 overexpression promotes phosphorylation of β‐catenin at Ser33/37, leading to a decreased β‐catenin protein level. Small hairpin RNA‐mediated ING5 knockdown significantly increased the β‐catenin level and inhibited phosphorylation of β‐catenin S33/37. Treatment with the WNT/β‐catenin inhibitor XAV939 inhibited ING5‐knockdown promoted proliferation, colony formation, migration, and invasion of lung cancer A549 cells, with increased phosphorylation of β‐catenin S33/37 and a decreased β‐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. Conclusion ING5 inhibits lung cancer invasion and EMT by inhibiting the WNT/β‐catenin pathway.https://doi.org/10.1111/1759-7714.13013Epithelial–mesenchymal transition (EMT)ING5lung cancerphosphorylationWNT/β‐catenin |
| spellingShingle | Xin‐Li Liu Jin Meng Xu‐Tao Zhang Xiao‐Hua Liang Feng Zhang Guan‐Ren Zhao Tao Zhang ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway Thoracic Cancer Epithelial–mesenchymal transition (EMT) ING5 lung cancer phosphorylation WNT/β‐catenin |
| title | ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway |
| title_full | ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway |
| title_fullStr | ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway |
| title_full_unstemmed | ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway |
| title_short | ING5 inhibits lung cancer invasion and epithelial–mesenchymal transition by inhibiting the WNT/β‐catenin pathway |
| title_sort | ing5 inhibits lung cancer invasion and epithelial mesenchymal transition by inhibiting the wnt β catenin pathway |
| topic | Epithelial–mesenchymal transition (EMT) ING5 lung cancer phosphorylation WNT/β‐catenin |
| url | https://doi.org/10.1111/1759-7714.13013 |
| work_keys_str_mv | AT xinliliu ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway AT jinmeng ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway AT xutaozhang ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway AT xiaohualiang ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway AT fengzhang ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway AT guanrenzhao ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway AT taozhang ing5inhibitslungcancerinvasionandepithelialmesenchymaltransitionbyinhibitingthewntbcateninpathway |