Secreted Frizzled Related Proteins: Implications in Cancers (BBA – Reviews on Cancer, Dec 2013)

The Wnt (wingless-type) signalling pathway plays an important role in embryonic development, tissue homeostasis, and tumour progression because of its effect on cell proliferation, migration, and differentiation. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signalling that act by binding directly to Wnt ligands or to Frizzled receptors. In recent years, aberrant expression of SFRPs has been reported to be associated with numerous cancers. As gene expression of SFRP members is often lost through promoter hypermethylation, inhibition of methylation through the use of epigenetic modifying agents could renew the expression of SFRP members and further antagonize deleterious Wnt signalling. Several reports have described epigenetic silencing of these Wnt signalling antagonists in various human cancers, suggesting their possible role as tumour suppressors. SFRP family members thus come across as potential tools in combating Wnt-driven tumourigenesis. However, little is known about SFRP family members and their role in different cancers. This review comprehensively covers all the available information on the role of SFRP molecules in various human cancers.



Rohit Surana1,2, Sakshi Sikka1,2, Wanpei Cai1,2, Eun Myoung Shin1, Sudha R. Warrier3, Hong Jie
Gabriel Tan1, Frank Arfuso4,6, Simon A. Fox5, Arun M. Dharmarajan4,6,*, Alan Prem Kumar1,2,6,7*

1Cancer Science Institute of Singapore, National University of Singapore, Singapore;
2Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;
3Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, India;
4School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia;
5Molecular Pharmacology Laboratory, School of Pharmacy, Western Australian Biomedical Research Institute & Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia;
6School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia 6845;
7Department of Biological Sciences, University of North Texas, Denton, TX 76203-5017, USA

Link to PubMed