DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways
Abstract Background Gastric cancer (GC) is one of the most common malignancies worldwide, particularly in China. DNA damage-inducible transcript 4 (DDIT4) is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses; however, its critical role in GC remains poorly underst...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-07-01
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| Series: | Cancer Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40880-018-0315-y |
| _version_ | 1811293241372311552 |
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| author | Feng Du Lina Sun Yi Chu Tingyu Li Chao Lei Xin Wang Mingzuo Jiang Yali Min Yuanyuan Lu Xiaodi Zhao Yongzhan Nie Daiming Fan |
| author_facet | Feng Du Lina Sun Yi Chu Tingyu Li Chao Lei Xin Wang Mingzuo Jiang Yali Min Yuanyuan Lu Xiaodi Zhao Yongzhan Nie Daiming Fan |
| author_sort | Feng Du |
| collection | DOAJ |
| description | Abstract Background Gastric cancer (GC) is one of the most common malignancies worldwide, particularly in China. DNA damage-inducible transcript 4 (DDIT4) is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses; however, its critical role in GC remains poorly understood. The present study aimed to investigate the potential relationship and the underlying mechanism between DDIT4 and GC development. Methods We used western blotting, real-time polymerase chain reaction, and immunohistochemical or immunofluorescence to determine DDIT4 expression in GC cells and tissues. High-content screening, cell counting kit-8 assays, colony formation, and in vivo tumorigenesis assays were performed to evaluate cell proliferation. Flow cytometry was used to investigate cell apoptosis and cell cycle distribution. Results DDIT4 was upregulated in GC cells and tissue. Furthermore, downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest. In contrast, ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity. Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation, and increased chemosensitivity upon DDIT4 downregulation. Conclusion DDIT4 promotes GC proliferation and tumorigenesis, providing new insights into the role of DDIT4 in the tumorigenesis of human GC. |
| first_indexed | 2024-04-13T04:58:30Z |
| format | Article |
| id | doaj.art-ee46f8e4cd55461e944c7d3a3c6520e1 |
| institution | Directory Open Access Journal |
| issn | 2523-3548 |
| language | English |
| last_indexed | 2024-04-13T04:58:30Z |
| publishDate | 2018-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Communications |
| spelling | doaj.art-ee46f8e4cd55461e944c7d3a3c6520e12022-12-22T03:01:25ZengWileyCancer Communications2523-35482018-07-0138111410.1186/s40880-018-0315-yDDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathwaysFeng Du0Lina Sun1Yi Chu2Tingyu Li3Chao Lei4Xin Wang5Mingzuo Jiang6Yali Min7Yuanyuan Lu8Xiaodi Zhao9Yongzhan Nie10Daiming Fan11State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityState Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityAbstract Background Gastric cancer (GC) is one of the most common malignancies worldwide, particularly in China. DNA damage-inducible transcript 4 (DDIT4) is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses; however, its critical role in GC remains poorly understood. The present study aimed to investigate the potential relationship and the underlying mechanism between DDIT4 and GC development. Methods We used western blotting, real-time polymerase chain reaction, and immunohistochemical or immunofluorescence to determine DDIT4 expression in GC cells and tissues. High-content screening, cell counting kit-8 assays, colony formation, and in vivo tumorigenesis assays were performed to evaluate cell proliferation. Flow cytometry was used to investigate cell apoptosis and cell cycle distribution. Results DDIT4 was upregulated in GC cells and tissue. Furthermore, downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest. In contrast, ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity. Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation, and increased chemosensitivity upon DDIT4 downregulation. Conclusion DDIT4 promotes GC proliferation and tumorigenesis, providing new insights into the role of DDIT4 in the tumorigenesis of human GC.http://link.springer.com/article/10.1186/s40880-018-0315-yDNA damage-inducible transcript 4Gastric cancerProliferationMitogen-activated protein kinasep53 |
| spellingShingle | Feng Du Lina Sun Yi Chu Tingyu Li Chao Lei Xin Wang Mingzuo Jiang Yali Min Yuanyuan Lu Xiaodi Zhao Yongzhan Nie Daiming Fan DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways Cancer Communications DNA damage-inducible transcript 4 Gastric cancer Proliferation Mitogen-activated protein kinase p53 |
| title | DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways |
| title_full | DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways |
| title_fullStr | DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways |
| title_full_unstemmed | DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways |
| title_short | DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways |
| title_sort | ddit4 promotes gastric cancer proliferation and tumorigenesis through the p53 and mapk pathways |
| topic | DNA damage-inducible transcript 4 Gastric cancer Proliferation Mitogen-activated protein kinase p53 |
| url | http://link.springer.com/article/10.1186/s40880-018-0315-y |
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