Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling

Yang, X; Xu, H; Yang, X; Wang, H; Zou, L; Yang, Q; Qi, X; Li, L; Duan, H; Yan, X; Fu, NY; Tan, J; Hou, Z; Jiao, B

Author(s): Yang, X; Xu, H; Yang, X; Wang, H; Zou, L; Yang, Q; Qi, X; Li, L; Duan, H; Yan, X; Fu, NY; Tan, J; Hou, Z; Jiao, B;
Details: Publication Year 2024-01-02,Volume 15,Issue #1,Page 36
Journal Title: Nature Communications
Abstract: While canonical Wnt signaling is well recognized for its crucial regulatory functions in cell fate decisions, the role of non-canonical Wnt signaling in adult stem cells remains elusive and contradictory. Here, we identified Mcam, a potential member of the non-canonical Wnt signaling, as an important negative regulator of mammary gland epithelial cells (MECs) by genome-scale CRISPR-Cas9 knockout (GeCKO) library screening. Loss of Mcam increases the clonogenicity and regenerative capacity of MECs, and promotes the proliferation, differentiation, and ductal morphogenesis of mammary epithelial in knockout mice. Mechanically, Mcam knockout recruits and polarizes macrophages through the Il4-Stat6 axis, thereby promoting secretion of the non-canonical Wnt ligand Wnt5a and its binding to the non-canonical Wnt signaling receptor Ryk to induce the above phenotypes. These findings reveal Mcam roles in mammary gland development by orchestrating communications between MECs and macrophages via a Wnt5a/Ryk axis, providing evidences for non-canonical Wnt signaling in mammary development.
Publisher: NPG
Keywords: Mice; Animals; *Wnt Proteins/genetics/metabolism; *Wnt Signaling Pathway; Wnt-5a Protein/genetics/metabolism; Cell Differentiation; Morphogenesis; Mice, Knockout; Macrophages/metabolism; Receptor Protein-Tyrosine Kinases/metabolism
Research Division(s): Cancer Biology And Stem Cells
PubMed ID: 38167296
Publisher's Version: https://doi.org/10.1038/s41467-023-44338-0
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-023-44338-0
Terms of Use/Rights Notice: Refer to copyright notice on published article.
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Creation Date: 2024-01-25 09:18:13

Last Modified: 2024-01-25 11:02:54