Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

• Published in: Cancer science Vol. 109; no. 11; pp. 3368 - 3375
• Main Authors: Yin, Ping, Wang, Wei, Zhang, Zhongbo, Bai, Yu, Gao, Jian, Zhao, Chenghai
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.11.2018; John Wiley and Sons Inc
• Subjects: Animals; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Catenin; Cell growth; Disease Progression; DKK; Embryos; Female; Frizzled protein; Frizzled Receptors - metabolism; FZD; Genes; Genotype & phenotype; Glycoproteins; Growth factors; Homeostasis; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; LDL-Receptor Related Proteins - metabolism; Ligands; Lipoproteins; LRP5 protein; Mammary Neoplasms, Animal - genetics; Mammary Neoplasms, Animal - metabolism; Metastasis; Mice; Mice, Transgenic; Phosphorylation; Proteins; Receptor density; Review; SFRP; Signal transduction; Stem cells; Transgenic animals; Transgenic mice; Tumors; Wnt; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway; β‐catenin; FZD; β-catenin; Wnt; DKK; SFRP
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13771

Wnt proteins, a group of secreted glycoproteins, mainly combine with receptors Frizzled (FZD) and/or low‐density‐lipoprotein receptor‐related proteins 5/6 (LRP5/6), initiating β‐catenin‐dependent and ‐independent signaling pathways. These pathways, which can be regulated by some secreted antagonists such as secreted Frizzled‐related proteins (SFRP) and dickkopf‐related protein (DKK), play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer. Wnt transgenic mice provide convincing evidence that Wnt signaling is involved in breast cancer initiation and progression, which is further strengthened by observations on human clinical breast cancer patients and studies on in vitro cultured human breast cancer cells. This review focuses on the roles of Wnt ligands, receptors and antagonists in breast cancer development instead of molecules or signaling transactivating β‐catenin independent on Wnt upstream components. Studies from Wnt transgenic mice and observations on human clinical patients indicate that Wnt upstream components contribute to the generation of tumor‐initiating cells and metastasis‐initiating cells, thereby inducing breast carcinogenesis and promoting breast metastasis, especially in basal‐like/triple‐negative breast cancers.