SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway

Chung, Ming Tzeung; Lai, Hung Cheng; Sytwu, Huey Kang; Yan, Ming; Shih, Yu Lueng; Chang, Chi-Ching; Mu, Yu; Liu, Hang Seng; Chu, Da W.; Lin, Yu-Shen

doi:10.1016/j.ygyno.2008.10.026

Cited by 132 publications

(104 citation statements)

References 39 publications

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“…These findings are consistent with those from other studies, which also reported a similar inverse correlation between the above proteins in endometrial, ovarian and breast cancer (37,38). The present findings, together with those from previous studies, suggest that sFRP2 may act as a tumor suppressor through its interaction with the Wnt canonical signaling pathway by modulating the cellular cytosolic pool of β-catenin (22). However, this causality is not completely clear yet; thus, future in vitro experiments where sFRP2 is knocked down are required to confirm this causality.…”

Section: E D C B Asupporting

confidence: 94%

“…It is therefore important to identify the aggressiveness of NFPAs for selection of the appropriate (30)(31)(32)(33)(34). sFRPs have been identified as possible antagonists of the Wnt signaling pathway, and sFRP2, a member of the sFRPs family, has been associated with the degree of tumor malignancy and invasive ability of various types of human cancer (20,22).…”

Section: Discussionmentioning

confidence: 99%

“…One class of such antagonists is the secreted frizzled-related protein (sFRP) family (16). The expression levels of sFRPs are inversely correlated with the grade and invasive ability of different tumors, including prostate, ovarian and cervical cancer, which suggests that sFRPs activities are fundamental for tissue homeostasis (17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

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Low expression of secreted frizzled-related protein 2 and nuclear accumulation of β-catenin in aggressive nonfunctioning pituitary adenoma

Bai

Hong

et al. 2016

Oncology Letters

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Abstract. The identification of a specific molecular marker for aggressiveness of nonfunctioning pituitary adenomas (NFPAs) is urgently required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, low expression of secreted frizzled-related protein 2 (sFRP2) in NFPAs was demonstrated by reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemical analyses. The results confirmed an abnormal accumulation of free β-catenin in the nuclei of NFPAs, which is the core step for the activation of the Wnt canonical signaling pathway. Furthermore, cyclin D1 and c-Myc, the downstream proteins of the Wnt canonical signaling pathway, were overexpressed in aggressive NFPAs. These findings demonstrated the activation of the Wnt canonical signaling pathway in aggressive NFPAs. In addition, sFRP2 expression was observed to be inversely correlated to the aggressiveness of NFPAs. Therefore, sFRP2 may act as a tumor suppressor through modulation of the cellular cytosolic pool of β-catenin in NFPAs. Furthermore, the expression of sFRP2 may serve as a biomarker for NFPAs aggressiveness and prognosis.

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Section: E D C B Asupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low expression of secreted frizzled-related protein 2 and nuclear accumulation of β-catenin in aggressive nonfunctioning pituitary adenoma

Bai

Hong

et al. 2016

Oncology Letters

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“…14 The tumor suppressor effect of SFRP1 and SFRP2 has been well studied in many cancers, [16][17][18][19] but SFRP5 has been investigated rarely. The functional role of SFRP5 relating to Wnt/b-catenin pathway in ovarian cancer remains unclear.…”

mentioning

confidence: 99%

Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway

Lai

Lin

et al. 2010

Intl Journal of Cancer

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156

110

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Oncogenic activation of the Wnt signaling pathway is common in cancers, but mutation of b-catenin in ovarian cancer is rare. In addition to genetic events, epigenetic modification of secreted frizzled-related protein (SFRP) family has been shown to be important in regulating Wnt signaling. Although high degree of homology is observed in the same family, different SFRPs may have opposing effects on the same process. We reported recently that a Wnt antagonist, SFRP5, is downregulated frequently through promoter hypermethylation and that this hypermethylation is associated with overall survival in ovarian cancer. The aim of this study was to analyze the function of SFRP5 in ovarian cancer. Functional assays including measuring cell proliferation, invasion, colony formation and xenograft were performed using ovarian cancer cell lines with overexpression of SFRP5 or a short hairpin RNA silencing. The methylation status of SFRP5 in relation to cisplatin resistance in ovarian cancer patients was analyzed. Restoration of the expression of SFRP5 attenuated Wnt signaling in ovarian cancer cells and suppressed cancer cell growth, invasion of cells and tumorigenicity in mice. These effects were independent of the canonical pathway. The expression of SFRP5 inhibited epithelial-mesenchymal transition (EMT). The restoration of SFRP5 downregulated AKT2 and sensitized ovarian cancer cells to chemotherapy. These effects are consistent with the poor response to platinumbased chemotherapy in patients with methylation of SFRP5. Our data suggested that epigenetic silencing of SFRP5 leads to oncogenic activation of the Wnt pathway and contributes to ovarian cancer progression and chemoresistance through the TWIST-mediated EMT and AKT2 signaling.Ovarian cancer is the second most common gynecological malignancy and the fifth leading cause of cancer-related death among women in the United States; nearly 60% of women with ovarian cancer eventually succumb to the disease.

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“…This gene belongs to the family of the secreted frizzled-related proteins (SFRP), which are able to downregulate Wnt signaling by forming an inhibitory complex with the Frizzled receptors. The role of SFRP1 as a tumor suppressor has been proposed in many other cancers (Caldwell, Jones et al 2004;Chung, Lai et al 2009). In gliomas, lower expression of SFPR1 and promoter hypermethylation has recently been reported (Götze, Wolter et al 2009).…”

Section: The Beta-catenin/wnt Pathwaymentioning

confidence: 99%

Genomic and Expression Alterations of Tumor Suppressor Genes in Meningioma Development, Progression and Recurrence

Pérez-Magán¹,

Rey²,

Meléndez³

et al. 2012

Tumor Suppressor Genes

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SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway

Cited by 132 publications

References 39 publications

Low expression of secreted frizzled-related protein 2 and nuclear accumulation of β-catenin in aggressive nonfunctioning pituitary adenoma

Low expression of secreted frizzled-related protein 2 and nuclear accumulation of β-catenin in aggressive nonfunctioning pituitary adenoma

Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway

Genomic and Expression Alterations of Tumor Suppressor Genes in Meningioma Development, Progression and Recurrence

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