Downregulation of SFRP5 expression and its inverse correlation with those of MMP-7 and MT1-MMP in gastric cancer

Zhao, Chenghai; Bu, Xianmin; Zhang, Ning; Wang, Wei

doi:10.1186/1471-2407-9-224

Cited by 34 publications

(32 citation statements)

References 37 publications

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“…This idea is supported by the cancer literature, which indicates that methylation and inactivation of SFRP5 is associated with ovarian, gastric, breast, and renal cancers as well as myeloid leukemia (58)(59)(60)(61)(62). However, Sfrp5 upregulation is absent in 3T3-L1 adipocytes treated with a demethylating agent (35).…”

Section: Discussionsupporting

confidence: 70%

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

Mori¹,

Prestwich²,

Reid³

et al. 2012

J. Clin. Invest.

144

160

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Preadipocytes secrete several WNT family proteins that act through autocrine/paracrine mechanisms to inhibit adipogenesis. The activity of WNT ligands is often decreased by secreted frizzled-related proteins (SFRPs). Sfrp5 is strongly induced during adipocyte differentiation and increases in adipocytes during obesity, presumably to counteract WNT signaling. We tested the hypothesis that obesity-induced Sfrp5 expression promotes the development of new adipocytes by inhibiting endogenous suppressors of adipogenesis. As predicted, mice that lack functional SFRP5 were resistant to diet-induced obesity. However, counter to our hypothesis, we found that adipose tissue of SFRP5-deficient mice had similar numbers of adipocytes, but a reduction in large adipocytes. Transplantation of adipose tissue from SFRP5-deficient mice into leptin receptor-deficient mice indicated that the effects of SFRP5 deficiency are tissue-autonomous. Mitochondrial gene expression was increased in adipose tissue and cultured adipocytes from SFRP5-deficient mice. In adipocytes, lack of SFRP5 stimulated oxidative capacity through increased mitochondrial activity, which was mediated in part by PGC1α and mitochondrial transcription factor A. WNT3a also increased oxygen consumption and the expression of mitochondrial genes. Thus, our findings support a model of adipogenesis in which SFRP5 inhibits WNT signaling to suppress oxidative metabolism and stimulate adipocyte growth during obesity.

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Section: Discussionsupporting

confidence: 70%

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

Mori¹,

Prestwich²,

Reid³

et al. 2012

J. Clin. Invest.

144

160

View full text Add to dashboard Cite

show abstract

“…It acts as soluble antagonist of Wnt signaling and is highly expressed in the retinal pigment epithelium, and moderately expressed in the pancreas ("Entrez Gene: SFRP5 secreted frizzled-related protein 5"). Previous studies has identified association of SFRP5 promoter hypermethylation with Acute myeloid leukemia [29], ovarian cancer [30], gastric cancer [31], oral squamous cell carcinoma [32], pancreatic cancer [33] and breast cancer [34]. …”

Section: Discussionmentioning

confidence: 99%

DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer

Zhu

Wang

Duan

et al. 2012

J Exp Clin Cancer Res

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BackgroundIt is well known that genetic alternation of epidermal growth factor receptor (EGFR) plays critical roles in tumorgenesis of lung cancer and can predict outcome of non-small-cell lung cancer treatment, especially the EGFR tyrosine-kinase inhibitors (EGFR-TKIs) therapy. However, it is unclear whether epigenetic changes such as DNA methylation involve in the response to the EGFR-TKI therapy.MethodsTumor samples from 155 patients with stages IIIB to IV NSCLC who received EGFR-TKI therapy were analyzed for DNA methylation status of Wnt antagonist genes, including SFRP1, SFRP2, SFRP5, DKK3, WIF1, and APC, using methylation specific PCR (MSP) method. EGFR mutations detections were performed in the same tissues samples using Denaturing High Performance Liquid Chromatography (DHPLC).ResultsWe found that Wnt antagonists tend to methylate simultaneously. Methylation of sFRP1 and sFRP5 are reversely correlated with EGFR mutation (P = 0.005, P = 0.011). However, no correlations of methylations of other Wnt antagonist genes with EGFR mutation were found. The patients with methylated SFRP5 have a significant shorter progression free survival than those with unmethylated SFRP5 in response to EGFR-TKI treatment (P = 0.002), which is independent of EGFR genotype.ConclusionsPatients with unmethylated SFRP5 are more likely to benefit from EGFR-TKI therapy.

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“…Primers for SFRP1, SFRP2 and SFRP5 methylated and unmethylated sequences were described in [14]. A demethylating agent, 5-Aza-2'-deoxycytidine (DAC, 2μmol/L, Sigma) was used to restore SFRP expression in cells with SFRP methylation [9]. In brief, cells were seeded at a density of 3×10 4 cells/cm 2 in a 24 well plate on day 0, and exposed to DAC on day 1, 2, and 3.…”

Section: Methodsmentioning

confidence: 99%

“…The pcDNA3.1 (Invitrogen, Paisley, United Kingdom) SFRP5 vector was made as described in [9]. For transfection experiments, 2×10 5 cells were plated in a 24-well plate 24 hours before transfection.…”

Section: Methodsmentioning

confidence: 99%

Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression

et al. 2012

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BackgroundAs one of the malignant tumors most often affecting children and young adults, Ewing sarcoma (ES) is characterized by early metastasis contributing to unfavorable prognosis. However, the molecular mechanisms responsible for ES metastasis remain poorly understood. In this study, we aimed to explore whether Wnt5a, a putative pro-metastatic factor, plays a role in ES metastasis.MethodsExpression of Wnt5a and CXCR4 was determined by real-time PCR or Western blot in 15 ES specimens and 4 ES cell lines, A-673, RD-ES, SK-N-MC and SK-ES-1. Expression of Wnt antagonists, SFRP1, SFRP2 and SFRP5, and some components in noncanonical Wnt pathway (p-JNK, p-cJUN and p-PKC) was also analyzed in this study. Methylation status of SFRP1, SFRP2 and SFRP5 was detected by Methylation-specific PCR (MSP). Wnt5a shRNA and pcDNA3.1 SFRP5 vector were used to abrogate Wnt5a expression and overexpress SFRP5 in ES cells, respectively.ResultsWnt5a expression was positively correlated with CXCR4 expression in ES specimens. Levels of both Wnt5a mRNA and CXCR4 mRNA were significantly higher in specimens from ES patients with metastasis at diagnosis compared with specimens from those without metastasis. Recombinant Wnt5a enhanced CXCR4 expression in ES cells, which was accompanied by increased ES cell migration, whereas Wnt5a shRNA has opposite effects. SFRP5 was methylated and silenced in ES cells, and both recombinant SFRP5 and pcDNA3.1 SFRP5 vector suppressed CXCR4 expression as well as ES cell migration. Wnt5a shRNA and recombinant SFRP5 inhibited phosphorylation of JNK and cJUN, and JNK inhibitor also reduced CXCR4 expression and cell migration in ES cells.ConclusionsWnt5a increases ES cell migration via upregulating CXCR4 expression in the absence of Wnt antagonist SFRP5, suggesting that Wnt5a overexpression and SFRP5 deficiency may jointly promote ES metastasis.

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Downregulation of SFRP5 expression and its inverse correlation with those of MMP-7 and MT1-MMP in gastric cancer

Cited by 34 publications

References 37 publications

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer

Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression

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