Disease relevance of SFRP1

• Therefore, epigenetic CpG hypermethylation of the SFRP1 promoter during chronic persistent inflammation and aging leads to the occurrence of gastrointestinal cancers, such as colorectal cancer and gastric cancer, through the breakdown of Hedgehog-dependent WNT signal inhibition [1].
• Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli [2].
• Here, we report significant transcriptional downregulation of the SFRP gene family in MM primary tissues and cell lines as well as several other cancer cell lines (breast, lung, glioma, and cervical) compared to normal cells [3].
• Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma [3].
• Modulated expression of secreted frizzled-related proteins in human retinal degeneration [4].

Psychiatry related information on SFRP1

• Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, OMIM 167400), is an inherited disease causing intense burning rectal, ocular, and submandibular pain and flushing [5].

High impact information on SFRP1

• Here we show that restoration of SFRP function in colorectal cancer cells attenuates WNT signaling even in the presence of downstream mutations [6].
• An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling [7].
• Anti-FRP-1 mAb immunoprecipitated gp80-85, gp120 and homodimers of these peptides, and anti-FRP-2 mAb reacted with gp135 identically to the alpha 3 subunit of integrin [8].
• Sfrp2 is known to modulate Wnt signaling, and we demonstrate that cardiomyocytes treated with secreted frizzled related protein increase cellular beta-catenin and up-regulate expression of antiapoptotic genes [9].
• FRZB encodes secreted frizzled-related protein 3, which is a soluble antagonist of wingless (wnt) signaling [10].

Chemical compound and disease context of SFRP1

• The mRNA expression of SFRP genes was quantified by real-time reverse-transcription PCR in esophageal adenocarcinoma cell lines with and without demethylation by 5-aza-2'deoxycytidine and inhibition of deacetylation by trichostatin A treatment [11].
• Expression of Frzb/secreted Frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasiveness [12].
• Lithium treatment of a small bowel mucosal cell line (FHs 74 int) induced sFRP1 within 8 h, indicating that this gene is positively regulated by beta-catenin, contrasting with the suppression of sFRP1 expression, we saw previously in advanced colorectal cancers [13].

Biological context of SFRP1

• SFRP1 methylation occurred in all BE samples and in 96% of EAC, while SFRP2 was methylated in 73% of the normal squamous esophageal mucosa samples [14].
• The chimpanzee SFRP1 gene was identified within the NW_110515.1 genome sequence [1].
• The GLI-binding site was identified within the human SFRP1 promoter based on bioinformatics and human intelligence [1].
• Furthermore, transfection of the SFRP gene construct into MM cell lines lacking SFRP expression resulted in apoptosis and growth suppression [3].
• Thus, role of sFRP as a negative regulator of Wnt signaling may have important implications in tumorigenesis, and its downregulation has been correlated with human cancers [3].

Anatomical context of SFRP1

• Hedgehog is secreted from differentiated epithelial cells to induce SFRP1 expression in mesenchymal cells, which keeps differentiated epithelial cells away from the effects of canonical WNT signaling [1].
• These facts indicate that SFRP1 is the Hedgehog target to confine canonical WNT signaling within stem or progenitor cells [1].
• Thus, photoreceptors are likely to be bathed by two opposing gradients of SFRP molecules [15].
• Cloning and characterization of a secreted frizzled-related protein that is expressed by the retinal pigment epithelium [15].
• Eight of the nine cancer cell lines we examined showed silencing of the SFRP family [3].

Associations of SFRP1 with chemical compounds

• Our data showed that SFRP1 was significantly up-regulated in cultured human PDLFs during ceramide-induced apoptosis [16].
• Secreted Frizzled-related protein 1 (SFRP1) encodes a member of a protein family that contains a cysteine-rich domain similar to the WNT-binding site of Frizzled receptors and regulates the WNT pathway [17].
• Demethylation treatment with 5-aza-2'-deoxycytidine in HCC cells restored SFRP1 expression [18].
• Bisulfite sequencing of SFRP1 demonstrated dense or patchy hypermethylation in tumor tissues that likely accounts for discrepant reported frequencies [19].
• This protein, called Frizzled-related protein (FRP), was first identified as a heparin-binding polypeptide that copurified with hepatocyte growth factor/scatter factor in conditioned medium from a human embryonic lung fibroblast line [20].

Regulatory relationships of SFRP1

• Anti-beta 2 integrin Ab blocked anti-FRP-1 Ab-induced cell aggregation, and anti-beta 1 integrin Ab and fibronectin inhibited anti-FRP-1 Ab-induced polykaryocyte formation [21].
• Consistent with this possibility, FrzA blocked elongation of ectodermal explants in response to activin, a potent mesoderm-inducing factor [22].
• In addition, we also detected that SFRP 1 inhibits the transcriptional activity of beta-catenin, which is thought to be a downstream molecule of SFRP 1, with luciferase reporter assay [23].
• Conversely, BMP-2 suppressed Wnt-10a and SFRP-1/SARP-2 [24].

Other interactions of SFRP1

• Cloning and sequencing of sarp2 and sarp3 revealed 38% and 40% sequence identity to sarp1, respectively [2].
• In conclusion, (1) alterations of key regulators of the Wnt signaling are frequent in the pathogenesis of BE; (2) the APC and SFRP1 genes are inactivated by promoter methylation in BE; (3) the WNT2 gene is upregulated along the progression from low-grade dysplasia to EAC [14].
• Here we examined expression of WNT and the WNT inhibitor, secreted frizzled-related protein (FRP), in RA and OA synovium by reverse transcription-PCR [25].
• We show aberrant DNA methylation and silencing of SFRP4, as well as of additional SFRP family members, in primary CLL samples [26].
• Promoter methylation of CDKN2A was infrequently detected in BE samples, while SFRP1 methylation was observed in all samples [27].

Analytical, diagnostic and therapeutic context of SFRP1

• Methylation-specific PCR (MSP) analysis showed that SFRP1, SFRP4, and SFRP5 gene promoters are frequently methylated in MM primary tissue (>80%) [3].
• We showed that a supraphysiological level of glucocorticoid enhanced SFRP1 but not LRP5 expression of primary mesenchymal cell cultures in vitro and osteoblasts at metaphyseal trabecular endosteum and chondrocytes at calcified cartilage in vivo [28].
• Results from chromatin immunoprecipitation indicate that Gli1 is involved in transcriptional regulation of sFRP-1 [29].
• Protein expression of SFRP genes was then assessed in these tissues by immunohistochemistry [11].
• We evaluated the hypermethylation of SARP2 in pure pancreatic juices (PPJ) aspirated endoscopically from patients with PCa, intraductal papillary mucinous neoplasm of the pancreas (IPMN), chronic pancreatitis (CP), and a control group who were consequently free of pancreatic diseases according to the differential diagnosis of PCa [30].

References