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

Cancer Sci. 2018 Nov;109(11):3368-3375. doi: 10.1111/cas.13771. Epub 2018 Sep 19.

Abstract

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.

Keywords: DKK; FZD; SFRP; Wnt; β-catenin.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Disease Progression
  • Female
  • Frizzled Receptors / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • LDL-Receptor Related Proteins / metabolism
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism*
  • Mice
  • Mice, Transgenic
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*

Substances

  • Frizzled Receptors
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins
  • WD repeat containing planar cell polarity effector
  • Wnt Proteins