The secreted Frizzled-related proteins (sFRPs) comprise a family of five secreted glycoproteins that may antagonize Wnt signaling through the binding and sequestering of Wnt ligands, and thus may have important implications in tumorigenesis. Both the downregulation and upregulation of sFRPs have been correlated with cancers.99 100 Moreover, in addition to genetic alterations, changes in the status of DNA methylation of the sFRP2 gene, known as epigenetic alterations, can be used as markers for colorectal cancer.101
Hypermethylation of the sFRPI gene on chromosome 8p12 is one of the earliest molecular alterations in colorectal carcinogenesis,102 103 potentially disrupting the Wnt signaling cascade of cellular growth control.102 sFRP1 expression is also frequently downregulated in bladder cancer.104 Restoration of sFRP function in colo-rectal cancer cells that have epigenic losses of sFRP function has been shown to attenuate Wnt signaling.96
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