Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT
Abstract Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the form...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-09-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04153-1 |
| _version_ | 1818582176685359104 |
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| author | Xing Kang En Xu Xingzhou Wang Lulu Qian Zhi Yang Heng Yu Chao Wang Chuanfu Ren Yizhou Wang Xiaofeng Lu Xuefeng Xia Wenxian Guan Tong Qiao |
| author_facet | Xing Kang En Xu Xingzhou Wang Lulu Qian Zhi Yang Heng Yu Chao Wang Chuanfu Ren Yizhou Wang Xiaofeng Lu Xuefeng Xia Wenxian Guan Tong Qiao |
| author_sort | Xing Kang |
| collection | DOAJ |
| description | Abstract Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance. |
| first_indexed | 2024-12-16T07:45:14Z |
| format | Article |
| id | doaj.art-7909f7d3b1dc462fbd353b02d590e246 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-16T07:45:14Z |
| publishDate | 2021-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-7909f7d3b1dc462fbd353b02d590e2462022-12-21T22:38:58ZengNature Publishing GroupCell Death and Disease2041-48892021-09-01121011110.1038/s41419-021-04153-1Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMTXing Kang0En Xu1Xingzhou Wang2Lulu Qian3Zhi Yang4Heng Yu5Chao Wang6Chuanfu Ren7Yizhou Wang8Xiaofeng Lu9Xuefeng Xia10Wenxian Guan11Tong Qiao12Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityDepartment of Vascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolAbstract Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.https://doi.org/10.1038/s41419-021-04153-1 |
| spellingShingle | Xing Kang En Xu Xingzhou Wang Lulu Qian Zhi Yang Heng Yu Chao Wang Chuanfu Ren Yizhou Wang Xiaofeng Lu Xuefeng Xia Wenxian Guan Tong Qiao Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT Cell Death and Disease |
| title | Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT |
| title_full | Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT |
| title_fullStr | Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT |
| title_full_unstemmed | Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT |
| title_short | Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT |
| title_sort | tenascin c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting erk triggered emt |
| url | https://doi.org/10.1038/s41419-021-04153-1 |
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