TGF-β1-induced RAP2 regulates invasion in pancreatic cancer
Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GT...
Main Authors: | , , , , , , , |
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Format: | Article |
Language: | English |
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China Science Publishing & Media Ltd.
2022-02-01
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Series: | Acta Biochimica et Biophysica Sinica |
Subjects: | |
Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022015 |
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author | Jin Kaizhou Liu Chen Cheng He Fei Qinglin Huang Qiuyi Xiao Zhiwen Yu Xianjun Wu Weiding |
author_facet | Jin Kaizhou Liu Chen Cheng He Fei Qinglin Huang Qiuyi Xiao Zhiwen Yu Xianjun Wu Weiding |
author_sort | Jin Kaizhou |
collection | DOAJ |
description | Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. In vitro studies demonstrated that silencing of RAP2 inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-β1 (TGF-β1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer. |
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id | doaj.art-04129bd9f5fa455294ad4c08251b015f |
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issn | 1672-9145 |
language | English |
last_indexed | 2024-03-11T12:25:18Z |
publishDate | 2022-02-01 |
publisher | China Science Publishing & Media Ltd. |
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series | Acta Biochimica et Biophysica Sinica |
spelling | doaj.art-04129bd9f5fa455294ad4c08251b015f2023-11-06T09:07:04ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-02-015436136910.3724/abbs.202201520d259ccTGF-β1-induced RAP2 regulates invasion in pancreatic cancerJin Kaizhou0Liu Chen1Cheng He2Fei Qinglin3Huang Qiuyi4Xiao Zhiwen5Yu Xianjun6Wu Weiding7["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]["Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China","Shanghai Pancreatic Cancer Institute, Shanghai 200032, China","Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China"]Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. In vitro studies demonstrated that silencing of RAP2 inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-β1 (TGF-β1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer.https://www.sciengine.com/doi/10.3724/abbs.2022015pancreatic cancerRAP2TGF-β1c-Mycinvasion |
spellingShingle | Jin Kaizhou Liu Chen Cheng He Fei Qinglin Huang Qiuyi Xiao Zhiwen Yu Xianjun Wu Weiding TGF-β1-induced RAP2 regulates invasion in pancreatic cancer Acta Biochimica et Biophysica Sinica pancreatic cancer RAP2 TGF-β1 c-Myc invasion |
title | TGF-β1-induced RAP2 regulates invasion in pancreatic cancer |
title_full | TGF-β1-induced RAP2 regulates invasion in pancreatic cancer |
title_fullStr | TGF-β1-induced RAP2 regulates invasion in pancreatic cancer |
title_full_unstemmed | TGF-β1-induced RAP2 regulates invasion in pancreatic cancer |
title_short | TGF-β1-induced RAP2 regulates invasion in pancreatic cancer |
title_sort | tgf β1 induced rap2 regulates invasion in pancreatic cancer |
topic | pancreatic cancer RAP2 TGF-β1 c-Myc invasion |
url | https://www.sciengine.com/doi/10.3724/abbs.2022015 |
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