SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect
Patients bearing liver metastasis of pancreatic adeno carcinoma (PDAC) suffer from poor prognosis due to its short duration and high mortality. Complex tumor microenvironment (TME) exists in liver metastatic niches, and tumor-associated macrophages (TAMs) have play vital roles in metastasis generati...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2023/3274467 |
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| _version_ | 1849412493657505792 |
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| author | Kun Wang Min He Xin Fan Jian Zhou Jian Yang Lin Wang Zhihong Zhao Chun Dai Zixiang Zhang |
| author_facet | Kun Wang Min He Xin Fan Jian Zhou Jian Yang Lin Wang Zhihong Zhao Chun Dai Zixiang Zhang |
| author_sort | Kun Wang |
| collection | DOAJ |
| description | Patients bearing liver metastasis of pancreatic adeno carcinoma (PDAC) suffer from poor prognosis due to its short duration and high mortality. Complex tumor microenvironment (TME) exists in liver metastatic niches, and tumor-associated macrophages (TAMs) have play vital roles in metastasis generation and outgrowth. We have discovered that M2 type TAM-derived SEMA5A could bind to its tumor cell-expressed receptor PLXNB3 to promote tumor cell proliferation and outgrowth. We utilized liver metastasis samples of PDAC patients, intrasplenic injection mouse models, and KrasG12D/Trp53R172H/Pdx1-Cre (KPC) mouse models for in vivo study. In mechanism investigation, we have discovered that SEMA5A-PLXNB3 axis could achieve tumor cell proliferation and survival via enhancing aerobic glycolysis termed as the Warburg effects. Targeting this axis may be a potential therapeutic approach for PDAC patients with unresectable liver metastasis. |
| format | Article |
| id | doaj-art-6484d1167e3f47daab718c3dcc562ec6 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-6484d1167e3f47daab718c3dcc562ec62025-08-20T03:34:25ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/3274467SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg EffectKun Wang0Min He1Xin Fan2Jian Zhou3Jian Yang4Lin Wang5Zhihong Zhao6Chun Dai7Zixiang Zhang8Department of General SurgeryDepartment of Biliary-Pancreatic SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryPatients bearing liver metastasis of pancreatic adeno carcinoma (PDAC) suffer from poor prognosis due to its short duration and high mortality. Complex tumor microenvironment (TME) exists in liver metastatic niches, and tumor-associated macrophages (TAMs) have play vital roles in metastasis generation and outgrowth. We have discovered that M2 type TAM-derived SEMA5A could bind to its tumor cell-expressed receptor PLXNB3 to promote tumor cell proliferation and outgrowth. We utilized liver metastasis samples of PDAC patients, intrasplenic injection mouse models, and KrasG12D/Trp53R172H/Pdx1-Cre (KPC) mouse models for in vivo study. In mechanism investigation, we have discovered that SEMA5A-PLXNB3 axis could achieve tumor cell proliferation and survival via enhancing aerobic glycolysis termed as the Warburg effects. Targeting this axis may be a potential therapeutic approach for PDAC patients with unresectable liver metastasis.http://dx.doi.org/10.1155/2023/3274467 |
| spellingShingle | Kun Wang Min He Xin Fan Jian Zhou Jian Yang Lin Wang Zhihong Zhao Chun Dai Zixiang Zhang SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect Journal of Immunology Research |
| title | SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect |
| title_full | SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect |
| title_fullStr | SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect |
| title_full_unstemmed | SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect |
| title_short | SEMA5A-PLXNB3 Axis Promotes PDAC Liver Metastasis Outgrowth through Enhancing the Warburg Effect |
| title_sort | sema5a plxnb3 axis promotes pdac liver metastasis outgrowth through enhancing the warburg effect |
| url | http://dx.doi.org/10.1155/2023/3274467 |
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