β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells
Background/Aims: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. Methods: We first kn...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/485013 |
| _version_ | 1818291368992178176 |
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| author | Wendan Yu Liren Li Fufu Zheng Wenjing Yang Shilei Zhao Chunfang Tian Wenwen Yin Yiming Chen Wei Guo Lijuan Zou Wuguo Deng |
| author_facet | Wendan Yu Liren Li Fufu Zheng Wenjing Yang Shilei Zhao Chunfang Tian Wenwen Yin Yiming Chen Wei Guo Lijuan Zou Wuguo Deng |
| author_sort | Wendan Yu |
| collection | DOAJ |
| description | Background/Aims: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. Methods: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of β-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. Results: β-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with β-catenin and contributed to β-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/β-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and β-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. Conclusions: Our study has provided new evidence for the role of β-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of β-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment. |
| first_indexed | 2024-12-13T02:42:58Z |
| format | Article |
| id | doaj.art-6dbaf28f672941cfa826e4ed37f01f47 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T02:42:58Z |
| publishDate | 2017-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-6dbaf28f672941cfa826e4ed37f01f472022-12-22T00:02:15ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-11-0144246747810.1159/000485013485013β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor CellsWendan YuLiren LiFufu ZhengWenjing YangShilei ZhaoChunfang TianWenwen YinYiming ChenWei GuoLijuan ZouWuguo DengBackground/Aims: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. Methods: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of β-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. Results: β-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with β-catenin and contributed to β-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/β-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and β-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. Conclusions: Our study has provided new evidence for the role of β-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of β-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.https://www.karger.com/Article/FullText/485013Prognosisβ-cateninCBPLung cancer |
| spellingShingle | Wendan Yu Liren Li Fufu Zheng Wenjing Yang Shilei Zhao Chunfang Tian Wenwen Yin Yiming Chen Wei Guo Lijuan Zou Wuguo Deng β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells Cellular Physiology and Biochemistry Prognosis β-catenin CBP Lung cancer |
| title | β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells |
| title_full | β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells |
| title_fullStr | β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells |
| title_full_unstemmed | β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells |
| title_short | β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells |
| title_sort | β catenin cooperates with creb binding protein to promote the growth of tumor cells |
| topic | Prognosis β-catenin CBP Lung cancer |
| url | https://www.karger.com/Article/FullText/485013 |
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