Sfrp2

What is SFRP2 protein?

SFRP2 (secreted frizzled related protein 2) gene is a protein coding gene which situated on the long arm of chromosome 4 at locus 4q31. This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. Methylation of this gene is a potential marker for the presence of colorectal cancer. The SFRP2 protein is consisted of 295 amino acids and its molecular mass is approximately 33.5 kDa.

What is the function of SFRP2 protein?

SFRP2 protein is a secreted protein, a member of the small molecule secreted protein family (SFRPs). It is involved in the biological processes of cell proliferation, differentiation, migration and apoptosis by binding to the regulatory factors of Wnt signaling pathway. Specifically, the SFRP2 protein can inhibit the activity of the Wnt signaling pathway, thereby affecting cell growth and differentiation, and is involved in regulating physiological and pathological processes such as tissue repair, inflammatory response, and cancer occurrence and development.

SFRP2 Related Signaling Pathway

SFRP2 protein is a secreted protein belonging to the SFRP family. It is involved in regulating the activity of Wnt signaling pathway by binding to regulatory factors of Wnt signaling pathway. Specifically, SFRP2 can competitively bind to the Wnt protein receptor complex, thereby inhibiting the activation of the Wnt signaling pathway. In addition, SFRP2 may also be involved in the regulation of other signaling pathways, such as Notch and Hedgehog. These signaling pathways play an important role in cell proliferation, differentiation, migration and other biological processes.

SFRP2 Related Diseases

Gene silencing caused by methylation of the SFRP2 gene promoter has been found in many cancers, such as colorectal, stomach, liver, breast, and lung cancers. The Wnt signaling pathway plays an important role in nervous system development and functional maintenance, so SFRP2 may have a potential impact in neurodegenerative diseases such as Alzheimer's disease. Wnt pathway is also related to the occurrence and development of metabolic diseases such as obesity and diabetes, and SFRP2 may play a role in the pathological mechanism of such diseases.

Fig1. Schematic of sFRP2 effects in melanoma cells exposed to aged or young fibroblasts. (Amanpreet Kaur, 2016)

Bioapplications of SFRP2

Researchers are exploring restoring or enhancing SFRP2 activity as a new anticancer strategy aimed at inhibiting cancer cell growth and metastasis. In protein-related disorders, regulating the Wnt signaling pathway may help control disease progression or promote tissue repair.

Case Study 1: Haoqing Yang, 2020

Mesenchymal stem cell (MSC)-based dental tissue regeneration is a potential treatment method in future, while inflammation and hypoxia niche will affect MSC-mediated tissue regeneration. In this research, the researchers intended to investigate the influence and mechanism of secreted frizzled-related protein 2(SFRP2) on MSC function under inflammation and hypoxia conditions.

Stem cells from apical papilla (SCAPs) were used in this study. The alkaline phosphatase (ALP) activity, Alizarin Red S staining, scratch-simulated wound migration and transwell chemotaxis assay were used to evaluate the functions of SFRP2. The Western blot, real-time RT-PCR and ChIP assays were used to evaluate the mechanism of SFRP2. Under inflammation and hypoxia conditions, the over-expression of SFRP2 could enhance the osteo/odontogenic differentiation ability. Mechanismly, SFRP2 inhibited canonical Wnt/β-catenin signalling pathway and then inhibited the target genes of nuclear factor kappa B (NFkB) signalling pathway.

Fig1. Real-time RT-PCR showed decreased SFRP2 expression in hypoxia with 10 ng/mL TNFα treatment.

Fig2. Western blot results showed phosphorylation of β-catenin in SCAPs-HA-SFRP2 and SCAPs-Vector in 3% hypoxia condition.

Case Study 2: Xianling Zeng, 2018

Choriocarcinoma (CC) is a highly aggressive gestational trophoblastic neoplasia; however, the underlying molecular mechanisms of its invasiveness and metastasis remain poorly understood. Human secreted frizzled-related protein 2 (SFRP2) could function as a tumor promoter or suppressor in different tumors, yet the role it plays in CC's invasion and metastasis is thoroughly unclear. The current study was aimed to explore the function and underlying mechanism of SFRP2 in CC.

The expression of SFRP2 in CC tissues was examined via immunohistochemistry. The methylation level and expression of SFRP2 in CC cell lines, JEG-3 and JAR were examined via bisulfite sequencing PCR (BSP), western blotting and quantitative RT-PCR. The biological role of increasing expressed SFRP2 through its promoter demethylation with 5-Aza-2'-deoxycytidine (5-Aza) was examined by a series of in vitro functional studies. The current study indicates that downregulated SFRP2 has potent tumor-promotive effects in CC through the modulation of cancer stemness and the EMT phenotype via activation of Wnt/β-catenin signaling in vitro and in vivo.

Fig3. Expression profiling of SFRP2 at the concentrations of 0, 1.25, 2.5, and 5 μM after 48 h treatment in JEG-3 and JAR cells at the protein level was analyzed by western blotting using cell lysates.

Fig4. Western blotting of SFRP2, Dvl3, β-catenin, p-GSK-3β, GSK-3β and EMT markers in JEG-3/ shSFRP2-1, JEG-3/shSFRP2-2 and JEG-3/vector sublines.

Sfrp2 has several biochemical functions, for example, NOT G-protein coupled receptor activity,NOT Wnt-activated receptor activity,Wnt-protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Sfrp2 itself. We selected most functions Sfrp2 had, and list some proteins which have the same functions with Sfrp2. You can find most of the proteins on our site.

Sfrp2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Sfrp2 here. Most of them are supplied by our site. Hope this information will be useful for your research of Sfrp2.

BUB1;PFKM;CDH1;EEF1G;CTNNA1;BMPR1A;DCC;SMAD4;DBNDD2;MLH3;RAD54B