Int J Biol Sci 2020; 16(6):1023-1034. doi:10.7150/ijbs.40535

Research Paper

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

Qing Liu1,2,3*, Jialin Song1,2,3*, Yue Pan4*, Dongdong Shi1,2,3, Chaogang Yang1,2,3, Shuyi Wang1,2,3, Bin Xiong1,2,3✉

1. Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
2. Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, China.
3. Hubei Cancer Clinical Study Center, Wuhan 430071, China.
4. Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
*These authors contributed equally to this work.

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Citation:
Liu Q, Song J, Pan Y, Shi D, Yang C, Wang S, Xiong B. Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression. Int J Biol Sci 2020; 16(6):1023-1034. doi:10.7150/ijbs.40535. Available from http://www.ijbs.com/v16p1023.htm

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Abstract

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 in vivo and in vitro. 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.

Keywords: tumor-associated macrophages, colorectal cancer, Wnt5a, CCL2