Secreted frizzled-related protein (SFRP)

Secreted frizzled-related protein is a member of a family of secreted glycoproteins characterized by a conserved cysteine-rich domain homologous to the Wnt-binding site of Frizzled receptors. SFRPs function as soluble antagonists of the Wnt signaling pathway by binding to extracellular Wnt ligands, thereby preventing these ligands from activating cell-surface Frizzled receptors and downstream β-catenin–dependent transcription. This regulatory activity is critical for embryonic development, cell differentiation, and maintaining tissue homeostasis. Loss or silencing of SFRPs, especially SFRP1, is associated with aberrant Wnt activation and development of several cancers, suggesting a tumor suppressor role. SFRPs are also implicated in the regulation of adipogenesis, metabolism, cardiovascular function, and possibly other diseases where Wnt signaling is perturbed. They are not cell-surface receptors themselves, but are soluble Wnt modulators whose therapeutic targeting remains experimental.

Other names

SFRPsFRPSecreted frizzled related proteinFRPSDF5FRZB

Antagonism of Wnt–Frizzled binding by direct binding to Wnt ligands, sequestering them from Frizzled receptors Inhibition of Wnt/β-catenin signaling resulting in decreased cell proliferation, cell cycle progression, and tumorigenesis Biphasic Wnt modulation: may suppress or, at low levels, potentiate Wnt signaling