Molecular strategies for modulating Wnt signaling.
The importance of the Wnt signaling cascade in the fields of developmental biology, regenerative medicine, cancer genetics, and neurobiology has fueled a wide search for potent pharmacological agents capable of controlling Wnt signaling. Numerous fields of study have lent assistance to this endeavor, yielding both natural and synthetic compounds that are capable of inducing or inhibiting Wnt at multiple stages within the pathway. Further, there is a large of body research which has investigated endogenous Wnt inducers and inhibitors, namely the secreted Wnts, Dickkof proteins, secreted Frizzled-Related Proteins, and Wnt Inhibitory Factor-1, along with others which may act via indirect means to stimulate or inhibit Wnt (e.g. the Smads, bone morphogenetic proteins, and Hedgehog proteins). This review will summarize the research surrounding currently available small molecules used to target Wnt signaling. These compounds will be classified based upon their ability to stimulate or inhibit Wnt, their derivation (natural or synthetic), and their specific mechanism of action.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55902, gustafson.carl@mayo.edu.
Carl T
CT
Gustafson
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55902.
Tewodros
T
Mamo
Department of Orthopaedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55902, and Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55902.
Avudaiappan
A
Maran
Department of Orthopaedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55902, and Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55902.
Michael J
MJ
Yaszemski
D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D047389:Casein Kinase I / Q000037:antagonists & inhibitors; D055808:Drug Discovery / Q000379:methods; D004705:Endocytosis / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D008954:Models, Biological; D038501:Tankyrases / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
D008565:Membrane Proteins; D051176:beta Catenin; D000217:Acyltransferases; C491188:PORCN protein, human; D038501:Tankyrases; D047389:Casein Kinase I; D019204:GTP-Binding Proteins