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: Kun Wang, Min He, Xin Fan, Jian Zhou, Jian Yang, Lin Wang, Zhihong Zhao, Chun Dai, Zixiang Zhang
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2023/3274467
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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.
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institution Kabale University
issn 2314-7156
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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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