Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression

Tumor-associated macrophages (TAMs) are closely correlated with tumor occurrence, invasion, and metastasis. However, factors affecting the biological functions of TAMs in colorectal cancer (CRC) are incompletely understood. Here, we found that Wnt5a was mainly expressed on TAMs of tumor stroma but n...

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Bibliographic Details
Published in:International journal of biological sciences 2020-01, Vol.16 (6), p.1023-1034
Main Authors: Liu, Qing, Song, Jialin, Pan, Yue, Shi, Dongdong, Yang, Chaogang, Wang, Shuyi, Xiong, Bin
Format: Article
Language:English
Subjects:
Antibodies
Ca2+/calmodulin-dependent protein kinase II
Cancer
Cell growth
Cell proliferation
Colorectal cancer
Colorectal carcinoma
Experiments
Extracellular signal-regulated kinase
Laboratory animals
Leukocyte migration
Macrophages
Metabolic pathways
Metastases
Metastasis
Monocyte chemoattractant protein 1
Paracrine signalling
Pore size
Proteins
Reagents
Research Paper
Roles
Secretion
Stroma
Therapeutic applications
Therapeutic targets
Tumor microenvironment
Tumorigenesis
Tumors
Wnt protein
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Summary:Tumor-associated macrophages (TAMs) are closely correlated with tumor occurrence, invasion, and metastasis. However, factors affecting the biological functions of TAMs in colorectal cancer (CRC) are incompletely understood. Here, we found that Wnt5a was mainly expressed on TAMs of tumor stroma but not on CRC cells. Subsequently, we found that Wnt5a TAMs facilitated tumor cell proliferation and migration, and recruited macrophages infiltration. Furthermore, Wnt5a knockdown impaired the pro-tumor roles of TAMs and . Mechanistically, the cancer-promoting roles of Wnt5a in TAMs depended on CaMKII-ERK pathway-mediated CCL2 secretion. Our data reveal the crucial role played by TAM-expressed Wnt5a in CRC tumorigenesis through paracrine secretion of CCL2. We first report the connection between Wnt5a/CaMKII/ERK/CCL2 axis and biological functions of TAMs in tumor microenvironment, indicating that Wnt5a may be a novel therapeutic target for CRC.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.40535