TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway
Abstract Background Aberrant expression of transcription Factor AP-2 Gamma (TFAP2C) has been reported to be implicated in malignant process of many cancers. The purpose of this study is to investigate the clinical significance and biological roles of TFAP2C in colorectal cancer (CRC). Methods TFAP2C...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0683-9 |
| _version_ | 1811334654333026304 |
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| author | Xu Wang Di Sun Jiandong Tai Si Chen Miao Yu Dong Ren Lei Wang |
| author_facet | Xu Wang Di Sun Jiandong Tai Si Chen Miao Yu Dong Ren Lei Wang |
| author_sort | Xu Wang |
| collection | DOAJ |
| description | Abstract Background Aberrant expression of transcription Factor AP-2 Gamma (TFAP2C) has been reported to be implicated in malignant process of many cancers. The purpose of this study is to investigate the clinical significance and biological roles of TFAP2C in colorectal cancer (CRC). Methods TFAP2C expression was evaluated by real-time PCR, Western blot and immunohistochemistry (IHC) respectively in clinical CRC tissues. Statistical analysis was performed to explore the correlation between TFAP2C expression and clinicopathological features, and overall and progression-free survival in CRC patients. In vitro and in vivo assays were performed to assess the biological roles of TFAP2C in CRC cells. Western blot, luciferase and Chromatin immunoprecipitation (ChIP) assays were used to identify the underlying pathway mediating the biological roles of TFAP2C in CRC. Results TFAP2C is robustly upregulated in CRC tissues and cells, and high expression of TFAP2C correlates with advanced clinicopathological features, poor prognosis and disease progression in CRC patients. Furthermore, upregulating TFAP2C enhances spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and reduces the apoptosis induced by 5-fluorouracil in colorectal cancer cells in vitro, and promotes stemness and chemoresistance of CRC cells in vivo; while silencing TFAP2C yields an opposite effect. Importantly, downregulation of TFAP2C dramatically restores chemotherapeutic sensitivity of CRC cells to 5-FU in vivo. Our results further demonstrate that TFAP2C promotes stemness and chemoresistance of CRC cells to 5-FU by inhibiting Hippo signaling via transcriptionally upregulating ROCK1 and ROCK2 in CRC cells. Conclusion Our findings indicate that TFAP2C may serve as a novel prognostic factor in CRC patients, and a therapeutic target for the treatment of CRC, suggesting that silencing TFAP2C in combination with 5-FU may be an effective therapeutic strategy to improve survival in CRC patients. |
| first_indexed | 2024-04-13T17:11:08Z |
| format | Article |
| id | doaj.art-d742f840c2fc4578a03469e31c1c7222 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T17:11:08Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-d742f840c2fc4578a03469e31c1c72222022-12-22T02:38:16ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-02-0137111610.1186/s13046-018-0683-9TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathwayXu Wang0Di Sun1Jiandong Tai2Si Chen3Miao Yu4Dong Ren5Lei Wang6Department of Colorectal and Anal Surgery, The First Hospital of Jilin UniversityDepartment of Colorectal and Anal Surgery, The First Hospital of Jilin UniversityDepartment of Colorectal and Anal Surgery, The First Hospital of Jilin UniversityDepartment of Colorectal and Anal Surgery, The First Hospital of Jilin UniversityCenter for Private Medical Service and Healthcare, The First Hospital of Sun Yat-sen UniversityDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Colorectal and Anal Surgery, The First Hospital of Jilin UniversityAbstract Background Aberrant expression of transcription Factor AP-2 Gamma (TFAP2C) has been reported to be implicated in malignant process of many cancers. The purpose of this study is to investigate the clinical significance and biological roles of TFAP2C in colorectal cancer (CRC). Methods TFAP2C expression was evaluated by real-time PCR, Western blot and immunohistochemistry (IHC) respectively in clinical CRC tissues. Statistical analysis was performed to explore the correlation between TFAP2C expression and clinicopathological features, and overall and progression-free survival in CRC patients. In vitro and in vivo assays were performed to assess the biological roles of TFAP2C in CRC cells. Western blot, luciferase and Chromatin immunoprecipitation (ChIP) assays were used to identify the underlying pathway mediating the biological roles of TFAP2C in CRC. Results TFAP2C is robustly upregulated in CRC tissues and cells, and high expression of TFAP2C correlates with advanced clinicopathological features, poor prognosis and disease progression in CRC patients. Furthermore, upregulating TFAP2C enhances spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and reduces the apoptosis induced by 5-fluorouracil in colorectal cancer cells in vitro, and promotes stemness and chemoresistance of CRC cells in vivo; while silencing TFAP2C yields an opposite effect. Importantly, downregulation of TFAP2C dramatically restores chemotherapeutic sensitivity of CRC cells to 5-FU in vivo. Our results further demonstrate that TFAP2C promotes stemness and chemoresistance of CRC cells to 5-FU by inhibiting Hippo signaling via transcriptionally upregulating ROCK1 and ROCK2 in CRC cells. Conclusion Our findings indicate that TFAP2C may serve as a novel prognostic factor in CRC patients, and a therapeutic target for the treatment of CRC, suggesting that silencing TFAP2C in combination with 5-FU may be an effective therapeutic strategy to improve survival in CRC patients.http://link.springer.com/article/10.1186/s13046-018-0683-9TFAP2CChemotherapeutic resistanceCancer stem cellsHippo signaling and colorectal cancer |
| spellingShingle | Xu Wang Di Sun Jiandong Tai Si Chen Miao Yu Dong Ren Lei Wang TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway Journal of Experimental & Clinical Cancer Research TFAP2C Chemotherapeutic resistance Cancer stem cells Hippo signaling and colorectal cancer |
| title | TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway |
| title_full | TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway |
| title_fullStr | TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway |
| title_full_unstemmed | TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway |
| title_short | TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway |
| title_sort | tfap2c promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway |
| topic | TFAP2C Chemotherapeutic resistance Cancer stem cells Hippo signaling and colorectal cancer |
| url | http://link.springer.com/article/10.1186/s13046-018-0683-9 |
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