FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression
Abstract Neuroblastoma (NB) is the most common and deadliest pediatric solid tumor. Targeting and reactivating tumor‐associated macrophages (TAMs) is necessary for reversing immune suppressive state and stimulating immune defense to exert tumoricidal function. However, studies on the function and re...
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doaj-c0ce641c3baf43e6a59dcecde31d014e2021-04-29T05:44:31ZengWileyClinical and Translational Medicine2001-13262021-04-01114n/an/a10.1002/ctm2.395FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progressionLei Miao0Zhenjian Zhuo1Jue Tang2Xiaomei Huang3Jiabin Liu4Hai‐Yun Wang5Huimin Xia6Jing He7Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou ChinaAbstract Neuroblastoma (NB) is the most common and deadliest pediatric solid tumor. Targeting and reactivating tumor‐associated macrophages (TAMs) is necessary for reversing immune suppressive state and stimulating immune defense to exert tumoricidal function. However, studies on the function and regulation of TAMs in NB progression are still limited. Fatty acid binding protein 4 (FABP4) in TAMs was correlated with advanced clinical stages and unfavorable histology of NB. FABP4‐mediated macrophages increased migration, invasion, and tumor growth of NB cells. Mechanically, FABP4 could directly bind to ATPB to accelerate ATPB ubiquitination in macrophages. The consequently decreased ATP levels could deactivate NF‐κB/RelA‐IL1α pathway, which subsequently results in macrophages reprogrammed to an anti‐inflammatory phenotype. We also demonstrated that FABP4‐enhanced migration and invasion were significantly suppressed by IL1α blocking antibody. Furthermore, circulating FABP4 was also associated with the clinical stages of NB. Our findings suggest that FABP4‐mediated macrophages may promote proliferation and migration phenotypes in NB cells through deactivating NF‐κB‐IL1α pathway by ubiquitinating ATPB. This study reveals the pathologic and biologic role of FABP4‐mediated macrophages in NB development and exhibits a novel application of targeting FABP4 in macrophages for NB treatment.https://doi.org/10.1002/ctm2.395FABP4neuroblastomatumor environmenttumor‐associated macrophages |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Miao Zhenjian Zhuo Jue Tang Xiaomei Huang Jiabin Liu Hai‐Yun Wang Huimin Xia Jing He |
spellingShingle |
Lei Miao Zhenjian Zhuo Jue Tang Xiaomei Huang Jiabin Liu Hai‐Yun Wang Huimin Xia Jing He FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression Clinical and Translational Medicine FABP4 neuroblastoma tumor environment tumor‐associated macrophages |
author_facet |
Lei Miao Zhenjian Zhuo Jue Tang Xiaomei Huang Jiabin Liu Hai‐Yun Wang Huimin Xia Jing He |
author_sort |
Lei Miao |
title |
FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression |
title_short |
FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression |
title_full |
FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression |
title_fullStr |
FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression |
title_full_unstemmed |
FABP4 deactivates NF‐κB‐IL1α pathway by ubiquitinating ATPB in tumor‐associated macrophages and promotes neuroblastoma progression |
title_sort |
fabp4 deactivates nf‐κb‐il1α pathway by ubiquitinating atpb in tumor‐associated macrophages and promotes neuroblastoma progression |
publisher |
Wiley |
series |
Clinical and Translational Medicine |
issn |
2001-1326 |
publishDate |
2021-04-01 |
description |
Abstract Neuroblastoma (NB) is the most common and deadliest pediatric solid tumor. Targeting and reactivating tumor‐associated macrophages (TAMs) is necessary for reversing immune suppressive state and stimulating immune defense to exert tumoricidal function. However, studies on the function and regulation of TAMs in NB progression are still limited. Fatty acid binding protein 4 (FABP4) in TAMs was correlated with advanced clinical stages and unfavorable histology of NB. FABP4‐mediated macrophages increased migration, invasion, and tumor growth of NB cells. Mechanically, FABP4 could directly bind to ATPB to accelerate ATPB ubiquitination in macrophages. The consequently decreased ATP levels could deactivate NF‐κB/RelA‐IL1α pathway, which subsequently results in macrophages reprogrammed to an anti‐inflammatory phenotype. We also demonstrated that FABP4‐enhanced migration and invasion were significantly suppressed by IL1α blocking antibody. Furthermore, circulating FABP4 was also associated with the clinical stages of NB. Our findings suggest that FABP4‐mediated macrophages may promote proliferation and migration phenotypes in NB cells through deactivating NF‐κB‐IL1α pathway by ubiquitinating ATPB. This study reveals the pathologic and biologic role of FABP4‐mediated macrophages in NB development and exhibits a novel application of targeting FABP4 in macrophages for NB treatment. |
topic |
FABP4 neuroblastoma tumor environment tumor‐associated macrophages |
url |
https://doi.org/10.1002/ctm2.395 |
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