Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling. Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake.

1. Data suggest that factors derived from conditioned medium of adipose-derived mesenchymal stem cells and sFRP4 significantly decrease cell viability and cell migration of breast tumor cells; this is accompanied by enhanced apoptosis via inhibition of canonical Wnt signal transduction. PMID: 29277675
2. increased SFRP4 and ficolin-3 levels are significantly associated with gestational diabetes mellitus development and might be important risk factors for this pregnancy complication. PMID: 29491225
3. High SFRP4 expression is associated with mesothelioma. PMID: 28534940
4. Epicardial adipose tissue and circulating SFRP4 expression levels were increased with patients with coronary artery disease. PMID: 29037197
5. Serum SFRP-4 levels were significantly higher in the type 2 diabetes group compared to the impaired glucose tolerance and normal glucose tolerance groups. PMID: 29455547
6. Studied role of Secreted Frizzled-Related Protein 4 (sFRP4) in angiostasis thru nitric oxide-cGMP cell signaling. PMID: 28267592
7. Progesterone regulated SFRP4 gene expression plays a role in uterine leiomyoma. PMID: 28637297
8. SFRP4 expression is significantly upregulated in human masticatory mucosa during wound healing PMID: 28005267
9. SFRP4 is significantly increased in patients with different types of diabetes. PMID: 26882051
10. Weak sFRP4 expression appeared to predict aggressive behavior, and was associated with recurrence/progression of GH-secreting pituitary adenomas. PMID: 26935389
11. A decreased risk of lung cancer was found for the genotype combination of DKK3 and sFRP4. PMID: 26457595
12. Down-regulation of SFRP4 is associated with recurrence in Endometrioid Adenocarcinoma. PMID: 26397159
13. proliferation of IGFBP5-mutated cancer cells is selectively blocked by IGF-1R inhibitors PMID: 26868304
14. concentrations of serum SFRP4 in T2DM and impaired glucose tolerance subjects were increased and were correlated closely with glycose metabolic disorder, the first-phase of glucose-stimulated insulin secretion and chronic low-grade inflammation PMID: 26041556
15. sFRP4 expression is inversely related to the aggressiveness of pituitary adenomas, and acts as a tumor suppressor. PMID: 24917361
16. Wnt3a can modulate intracellular localisation and secretion of sFRP4. PMID: 25805505
17. We found that miR-203 was significantly downregulated in OSF tissues compared to that in normal buccal mucosa tissues, and that miR-203 negatively regulated secreted SFRP4 and positively regulated TM4SF1 PMID: 25872484
18. Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (p<5x10(-6) as compared to both PCOS groups). PMID: 25089371
19. Abdominal adipose tissue is a major contributor for circulating-SFRP4; SFRP4 has an important role in obese adipose tissue pathophysiology. PMID: 25322919
20. SFRP4 concentrations are associated with impaired glucose and triglyceride metabolism PMID: 25408147
21. findings suggest that an epigenetic event is critically involved in the pathogenesis of psoriasis, and the downregulation of SFRP4 by CpG island methylation is one possible mechanism contributing to the hyperplasia of epidermis in the disease PMID: 25825452
22. Increased SFRP4 expression may not always correlate with an increase in apoptosis, possibly due to the complex interactions between different signalling pathways. [Review] PMID: 25501511
23. total of three potential inhibitors of SFRP4 were found, namely cyclothiazide, clopamide and perindopril. These inhibitors showed significant interactions with SFRP4 as compared to other inhibitors as well as control (acetohexamide). PMID: 25019556
24. Our results suggest that the sFRP3 c.970C>G and sFRP4 c.958C>A polymorphisms may be genetic factors associated with the prevalence of osteoporosis at the femoral neck in postmenopausal Korean women. PMID: 24662300
25. High SFRP4 gene methylation is associated with ovarian cancer infected with high risk human papillomavirus. PMID: 24761891
26. ZAR1 and SFRP4 qMSP could be used as potential biomarker for CC diagnosis PMID: 24787227
27. Decreased placental expression of Wnt2 and increased placental expression of sFRP4 may be associated with the pathogenesis of severe preeclampsia. PMID: 23322712
28. This raises the possibility that SFRP4 may be used both diagnostically and therapeutically in epithelial ovarian cancer. PMID: 23326605
29. SFRP4 caused reduced glucose tolerance through decreased islet expression of Ca(2+) channels and suppressed insulin exocytosis. PMID: 23140642
30. haplotype genotypes of secreted frizzled-related protein 4 (sFRP4) c.958C>A and c.1019G>A polymorphisms are genetic factors that affect changes in bone mineral density of the femoral neck after hormone therapy in postmenopausal Korean women PMID: 22668815
31. sFRP4's cysteine-rich domain was seen to inhibit tube formation of endothelial cells. In addition, the netrin-like domain promoted endothelial cell death and may also inhibit angiogenesis. PMID: 23035359
32. genetic variation in sFRP4 has an influence on hip fracture risk, percentage body fat and height in a Danish male population. However, we were unable to replicate these results in an independent Belgian population. PMID: 22608881
33. These results support a role for SFRP4 as a tumor suppressor gene in ovarian cancers. PMID: 22363760
34. Data show that decidualization was associated with increased expression of 428 genes including SCARA5 (181-fold), DKK1 (71-fold) and PROK1 (32-fold), and decreased expression of 230 genes including MMP-7 (35-fold) and SFRP4 (21-fold). PMID: 21858178
35. results indicate that the coding regions of INHBA, SFRP4 and HOXA10 do not harbour mutations responsible for linkage to endometriosis in the families studied PMID: 21576276
36. sFRP4 is expressed in human GCs and its expression declines during late antral follicular growth PMID: 21307090
37. Methylation and unmethylation of SFRP4 were both detected in CA46, HL60 and U937 cell lines. PMID: 20030932
38. the secreted frizzled-related protein (sFRP4) c1019G>A polymorphism may be one of the genetic factors affecting lumbar spine Bone minera density in postmenopausal Korean women. Risk AA genotype was 6.39 times higher than GG PMID: 20613673
39. SFRP4 promoter methylation is aberrant in mesothelioma. PMID: 20596629
40. sFRP-4 displays phosphatonin-like properties. PMID: 12952927
41. lack of secreted frizzled-related protein 4 leads to progression of prostate cancer PMID: 14760084
42. Methylation silencing of SFRP4 may play an important role in aberrant Wnt activation in mesothelioma even in the absence of beta-catenin PMID: 15705870
43. sFRP-4 increases renal P(i) excretion by reducing Na(+)-P(i)-IIa transporter abundance in the brush border of the proximal tubule through enhanced internalization of the protein. PMID: 16151791
44. In contrast to other sFRP family members, sFRP-4 expression appears to be upregulated in colorectal carcinoma PMID: 16356838
45. The SFRP4 protein gene plays an important role in the pathogenesis of bladder tumor and can be detected using cellular DNA extracted from urine samples. PMID: 16609023
46. sFRP4 is an inhibitor of prostate cancer growth and invasion in vitro independent of androgen receptor (AR) signaling. PMID: 17476687
47. These data suggest sFRP4 promotes epidermal differentiation. PMID: 18938133
48. sFRP4 may be a potential biomarker for monitoring the progression of ADPKD. PMID: 18945944
49. Dkk1 and sFRP4 perform an important function in adipogenesis in human adipose tissue-derived mesenchymal stem cells. PMID: 19040566
50. sFRP4 has a role in placental development and implantation, and may be an important factor in the development of the decidual fibrinoid zone, and in trophoblast apoptosis and a band of apoptosis in the underlying decidua deep into the trophoblast. PMID: 19146776

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Secreted. Note=Cytoplasmic in ovarian tumor cells.

Secreted frizzled-related protein (sFRP) family

Expressed in mesenchymal cells. Highly expressed in the stroma of proliferative endometrium. Expressed in cardiomyocytes. Shows moderate to strong expression in ovarian tumors with expression increasing as the tumor stage increases. In ovarian tumors, exp

HGNC: 10778

OMIM: 265900

KEGG: hsa:6424

STRING: 9606.ENSP00000410715

UniGene: Hs.658169