The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells.
Aberrant Wnt/β-catenin signaling is implicated in tumorigenesis and the progression of human colorectal cancers, and mutations in the components of the Wnt/β-catenin signaling pathway are observed in the majority of patients. Therefore, extensive studies on the Wnt signaling pathway and its target g...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6028230?pdf=render |
| _version_ | 1818420242215337984 |
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| author | Makoto Inoue Yohei Uchida Makoto Edagawa Manabu Hirata Jun Mitamura Daiki Miyamoto Kenji Taketani Shigeki Sekine Junya Kawauchi Shigetaka Kitajima |
| author_facet | Makoto Inoue Yohei Uchida Makoto Edagawa Manabu Hirata Jun Mitamura Daiki Miyamoto Kenji Taketani Shigeki Sekine Junya Kawauchi Shigetaka Kitajima |
| author_sort | Makoto Inoue |
| collection | DOAJ |
| description | Aberrant Wnt/β-catenin signaling is implicated in tumorigenesis and the progression of human colorectal cancers, and mutations in the components of the Wnt/β-catenin signaling pathway are observed in the majority of patients. Therefore, extensive studies on the Wnt signaling pathway and its target genes are crucial to understand the molecular events of tumorigenesis and develop an efficacious therapy. In this study, we showed that the stress response gene ATF3 is transcriptionally activated by the binding of β-catenin and TCF4 to the redundant TCF4 site at the proximal promoter region of the ATF3 gene, indicating that ATF3 is a direct target of the Wnt/β-catenin pathway. The loss of function or overexpression studies showed that ATF3 inhibited the migration or invasion of HCT116 cells. The expression of some MMP and TIMP genes and the ratio of MMP2/9 to TIMP3/4 mRNAs was differentially regulated by ATF3. Therefore, though ATF3 is activated downstream of the Wnt/β-catenin pathway, it acts as a negative regulator of the migration and invasion of HCT116 human colon cancer cells exhibiting aberrant Wnt/β-catenin activity. ATF3 is a candidate biomarker and target for human colorectal cancer treatment and prevention. |
| first_indexed | 2024-12-14T12:51:21Z |
| format | Article |
| id | doaj.art-afe884ea762048ca8a7b5767cf0943e1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T12:51:21Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-afe884ea762048ca8a7b5767cf0943e12022-12-21T23:00:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e019416010.1371/journal.pone.0194160The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells.Makoto InoueYohei UchidaMakoto EdagawaManabu HirataJun MitamuraDaiki MiyamotoKenji TaketaniShigeki SekineJunya KawauchiShigetaka KitajimaAberrant Wnt/β-catenin signaling is implicated in tumorigenesis and the progression of human colorectal cancers, and mutations in the components of the Wnt/β-catenin signaling pathway are observed in the majority of patients. Therefore, extensive studies on the Wnt signaling pathway and its target genes are crucial to understand the molecular events of tumorigenesis and develop an efficacious therapy. In this study, we showed that the stress response gene ATF3 is transcriptionally activated by the binding of β-catenin and TCF4 to the redundant TCF4 site at the proximal promoter region of the ATF3 gene, indicating that ATF3 is a direct target of the Wnt/β-catenin pathway. The loss of function or overexpression studies showed that ATF3 inhibited the migration or invasion of HCT116 cells. The expression of some MMP and TIMP genes and the ratio of MMP2/9 to TIMP3/4 mRNAs was differentially regulated by ATF3. Therefore, though ATF3 is activated downstream of the Wnt/β-catenin pathway, it acts as a negative regulator of the migration and invasion of HCT116 human colon cancer cells exhibiting aberrant Wnt/β-catenin activity. ATF3 is a candidate biomarker and target for human colorectal cancer treatment and prevention.http://europepmc.org/articles/PMC6028230?pdf=render |
| spellingShingle | Makoto Inoue Yohei Uchida Makoto Edagawa Manabu Hirata Jun Mitamura Daiki Miyamoto Kenji Taketani Shigeki Sekine Junya Kawauchi Shigetaka Kitajima The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. PLoS ONE |
| title | The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. |
| title_full | The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. |
| title_fullStr | The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. |
| title_full_unstemmed | The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. |
| title_short | The stress response gene ATF3 is a direct target of the Wnt/β-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells. |
| title_sort | stress response gene atf3 is a direct target of the wnt β catenin pathway and inhibits the invasion and migration of hct116 human colorectal cancer cells |
| url | http://europepmc.org/articles/PMC6028230?pdf=render |
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