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

International Journal of Biological Sciences
Qing LiuBin Xiong

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.

Citations

May 22, 2020·Cancer Metastasis Reviews·Pablo Lopez-Bergami, Gastón Barbero
Oct 22, 2020·International Journal of Molecular Sciences·Malvina KoniMaria Felice Brizzi
Nov 25, 2020·Archives of Pharmacal Research·Ji-Hak JeongYou Mie Lee
Mar 25, 2021·Cancer Management and Research·Guangshun SunWeiwei Tang
Jun 5, 2021·Journal of Cell Communication and Signaling·Arun J Singh, Joe W Gray

❮ Previous
Next ❯

Methods Mentioned

BETA
PMA
PCR
xenograft
transfection
ELISA

Software Mentioned

SPSS

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Xiaoming ZhongZhiwen Yang
Lung Cancer : Journal of the International Association for the Study of Lung Cancer
L A LievenseJ P J J Hegmans
© 2021 Meta ULC. All rights reserved