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

Zi, Xiaolin; Guo, Yi; Simoneau, Anne R.; Hope, Christopher; Xie, Jun; Holcombe, Randall F.; Hoang, Bang H.

doi:10.1158/0008-5472.can-05-0103

Cited by 173 publications

(160 citation statements)

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“…SFRP3, another Wnt pathway antagonist, reduces activity of metalloproteinases and activation of β-catenin and thus inhibits epithelial-mesenchymal transition (EMT) seen in several cancer types [22,23]. We observed statistically significant decreased of the amount of SFRP3 protein expression in our total renal cancer clear cell tumors compared with normal kidney tissues.…”

Section: Discussionmentioning

confidence: 55%

Expression of Secreted Frizzled-Related Protein 1 and 3, T-cell Factor 1 and Lymphoid Enhancer Factor 1 in Clear Cell Renal Cell Carcinoma

Nikuševa-Martić

Šerman

Zeljko

et al. 2013

Pathol. Oncol. Res.

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Frequency and mortality of renal cell carcinoma (RCC) are increasing for decades. However, the molecular background of RCC tumorigenesis is still poorly understood. In current study we investigated the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3)to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC).36 pairs of paraffin-embedded clear cRCC and adjacent nontumoral tissues samples using immunohistochemistry (IHC) were analyzed and compared with corresponding clinicopathological parameters.Immunohistochemistry indicated statistically significant decreased SFRP3 expression in tumor tissues but no consistency in SFRP1 expression in analyzed normal and tumor tissue.The TCF1 expression level was significantly weaker in normal tissue compared to tumor samples while LEF1 protein levels were significantly weaker in tumor tissue.To our knowledge, this is the first report on analysis of the expression of transcription factors TCF1 and LEF1 in clear cell renal cell carcinoma and their comparison with Wnt signal pathway antagonists belonging to SFRP family.

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Section: Discussionmentioning

confidence: 55%

Expression of Secreted Frizzled-Related Protein 1 and 3, T-cell Factor 1 and Lymphoid Enhancer Factor 1 in Clear Cell Renal Cell Carcinoma

Nikuševa-Martić

Šerman

Zeljko

et al. 2013

Pathol. Oncol. Res.

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“…In line with a tumour suppressor function of SFRPs, loss or significant downregulation of SFRP1 or SFRP3 expression has been observed in a large proportion of invasive carcinomas, such as in breast (Turashvili et al, 2006;Zhou et al, 1998), gastric , cervical (Ko et al, 2002), hepatocellular (Huang et al, 2007) and prostate (Zi et al, 2005) tumours. Conversely, restoring SFRP expression in various cancer cells attenuates their tumorigenic behaviour (Zi et al, 2005), decreases β-catenin stabilisation and promotes cell death even when downstream components of the canonical pathway are mutated .…”

Section: The Roles Of Sfrps In Pathological Eventsmentioning

confidence: 83%

Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease

Bovolenta

Esteve

Ruiz

et al. 2008

Journal of Cell Science

547

523

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types of cancers, bone pathologies, retinal degeneration and hypophosphatemic diseases, indicating that their activity is fundamental for tissue homeostasis. Here we review some of the debated aspects of SFRP-Wnt interactions and discuss the new and emerging roles of SFRPs. Journal of Cell Science 738 were isolated either through sequence homology with Fz receptors (Rattner et al., 1997) or, independently of Wnt activity, through their involvement in apoptosis (Melkonyan et al., 1997), or their co-purification with the heparin-binding factor hepatocyte growth factor/scattered factor (Finch et al., 1997).Since their discovery, interest in this family of molecules has grown progressively, particularly because recent observations have offered a new perspective on their functions and mechanisms of action in both development and disease. These studies indicate that SFRPs are not merely Wnt-binding proteins but can also antagonise one another's activity (Yoshino et al., 2001), bind to Fz receptors (Bafico et al., 1999;Rodriguez et al., 2005) and provide axon-guidance information (Rodriguez et al., 2005). Moreover, they can interact with other receptors or matrix molecules (Chuman et al., 2004;Hausler et al., 2004; and interfere with BMP signalling (Lee, H. et al., 2006;Muraoka et al., 2006;Yabe et al., 2003) by acting as proteinase inhibitors (Lee, H. et al., 2006). Furthermore, their expression is altered in different types of cancers (Rubin et al., 2006), in bone pathologies , retinal degeneration (Jones et al., 2000) and hypophosphatemic diseases (Berndt and Kumar, 2007), which indicates that their activity is fundamental for tissue homeostasis. Reviews that centre on Wnt antagonism by SFRPs have recently been published elsewhere (Cadigan and Liu, 2006;Jones and Jomary, 2002;Kawano and Kypta, 2003); here, we discuss new aspects of SFRP activity, and review SFRP structure, expression and interactions with Wnt proteins. The family of SFRPsThe SFRP family comprises five members in humans, SFRP1 to SFRP5, in which SFRP3 is the orthologue of the founding member Frzb. Sequence comparison and phylogenetic analysis show that SFRP1, SFRP2 and SFRP5 are closely related, and cluster together in a subgroup that diverges from the one formed by the related SFRP3 and SFRP4 (Fig. 1). This clustering also reflects a different genomic organisation. SFRP1, SFRP2 and SFRP5 are encoded by three exons on chromosome 8p12-p11.1, 4q31.3 and 10q24.1, respectively (Garcia-Hoyos et al., 2004), whereas SFRP3 and SFRP4 are both encoded by six exons -on chromosome 2q31-q33 and 7p14-p13, respectively. Orthologues of the five human genes have been found in all vertebrate species analysed so far ( Fig. 1). Notably, a third subgroup, apparently not present in mammals, has been identified in Xenopus, zebrafish and chick. The components of this subgroup, named Sizzled, Crescent and Tlc, share sequence similarities with the SFRP1-SFRP2-SFRP5 subgroup (Fig. 1), and are characterised by a very restricted and anterior expression in gastrulating embryos (B...

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“…MMP-9 plays an important role in tumor cell invasion, metastasis, and angiogenesis (45), but no relationship was found between ARH-GEF5 and MMP-9. It should be noted that MMP expression is modulated by activation of AKT, MAPK, and NF-kB (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation

Yang

et al. 2015

Molecular Cancer Therapeutics

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We sought to elucidate the role of Rho guanine nucleotide exchange factor 5 (ARHGEF5) in tumorigenesis of lung adenocarcinoma cells. ARHGEF5 protein levels were assessed in 91 human lung adenocarcinoma specimens, and A549 and NCI-H1650 cells, by IHC and Western blotting. In addition, ARHGEF5 mRNA expression was evaluated by quantitative reverse transcriptase-PCR. Furthermore, ARHGEF5 long and short isoform coexpression was detected by immunofluorescence. Finally, flow cytometry; CCK8 and wound-healing assays; cell invasion, migration and adhesion; and xenografts were used to evaluate the biologic significance of ARHGEF5. ARHGEF5 was significantly increased in lung adenocarcinoma tissues and cell lines. Interestingly, ARHGEF5 levels were significantly associated with tumor grade and pathologic stage, but not age, gender, T stage, or lymph node metastasis status. ARHGEF5 knockdown by RNAi resulted in dramatically reduced proliferation, adhesion, invasion, and migratory capability of A549 and NCI-H1650 cells. Likewise, protein levels of p-Src, p-Akt, and NF-kB were significantly decreased after ARHGEF5 knockdown. In parallel, increased S-phase population and MMP-2/cyclin D1 expression were observed in the cancer cells, which were not apoptotic. In addition, ARHGEF5 knockdown A549 and NCI-H1650 cells injected s.c. and i.v. into nude mice exhibited decreased xenograft volume and overtly reduced metastasis. Conversely, ARH-GEF5 overexpression in A549 and NCI-H1650 cells increased their tumorigenicity in vitro. ARHGEF5 acts as a proto-oncogene in human lung adenocarcinoma cell tumorigenesis.

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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

Cited by 173 publications

References 44 publications

Expression of Secreted Frizzled-Related Protein 1 and 3, T-cell Factor 1 and Lymphoid Enhancer Factor 1 in Clear Cell Renal Cell Carcinoma

Expression of Secreted Frizzled-Related Protein 1 and 3, T-cell Factor 1 and Lymphoid Enhancer Factor 1 in Clear Cell Renal Cell Carcinoma

Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease

Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation

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