Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells
The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.593685/full |
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| author | Guo Pin Guo Pin Li Huanting Zhu Chengzhan Kong Xinjuan Feng Yugong Liu Wei Li Shifang Li Zhaojian Han Kun Yao Weicheng Lin Yingying Qiu Yongming Yu Yanan |
| author_facet | Guo Pin Guo Pin Li Huanting Zhu Chengzhan Kong Xinjuan Feng Yugong Liu Wei Li Shifang Li Zhaojian Han Kun Yao Weicheng Lin Yingying Qiu Yongming Yu Yanan |
| author_sort | Guo Pin |
| collection | DOAJ |
| description | The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials. |
| first_indexed | 2024-12-12T00:32:15Z |
| format | Article |
| id | doaj.art-b6cadeeacdea4bcca1b337a0a8f097c2 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T00:32:15Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b6cadeeacdea4bcca1b337a0a8f097c22022-12-22T00:44:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.593685593685Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma CellsGuo Pin0Guo Pin1Li Huanting2Zhu Chengzhan3Kong Xinjuan4Feng Yugong5Liu Wei6Li Shifang7Li Zhaojian8Han Kun9Yao Weicheng10Lin Yingying11Qiu Yongming12Yu Yanan13Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaInstitute of Cerebral Vascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaThe programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.https://www.frontiersin.org/articles/10.3389/fcell.2020.593685/fullgliomaPDCD4AKTSTAT3angiogenesis |
| spellingShingle | Guo Pin Guo Pin Li Huanting Zhu Chengzhan Kong Xinjuan Feng Yugong Liu Wei Li Shifang Li Zhaojian Han Kun Yao Weicheng Lin Yingying Qiu Yongming Yu Yanan Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells Frontiers in Cell and Developmental Biology glioma PDCD4 AKT STAT3 angiogenesis |
| title | Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells |
| title_full | Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells |
| title_fullStr | Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells |
| title_full_unstemmed | Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells |
| title_short | Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells |
| title_sort | down regulation of pdcd4 promotes proliferation angiogenesis and tumorigenesis in glioma cells |
| topic | glioma PDCD4 AKT STAT3 angiogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.593685/full |
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