Disease relevance of FZD7

• Among seven gastric cancer cell lines, FZD7 was up-regulated in MKN7, which was consistent with a previous report [1].
• Using the ectodomain as an antagonist we have modulated endogenous FZD7 signalling in the moderately differentiated colon adenocarcinoma cell line, SK-CO-1 [2].
• FZD7, expressed in the normal gastrointestinal tract, is upregulated in esophageal cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma [3].
• In the present study, a quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for FZD7 was developed and overexpression of FZD7 was detected in 90% of tumors, most of which were related to chronic hepatitis B virus infection [4].
• Among human esophageal and gastric cancer cell lines, expression level of FZD7 was relatively lower in esophageal cancer cell lines, and was highest in the gastric cancer cell line MKN7 [5].

High impact information on FZD7

• FZD7 also was overexpressed in the 6 HCC cell lines tested and functional analysis showed that FZD7 messenger RNA (mRNA) levels correlated with enhanced cellular motility [4].
• RESULTS: Transfection of HCC cells with dominant-negative mutant constructs encoding a C-terminally truncated FZD7 protein decreased wild-type beta-catenin protein accumulation and reduced cell motility [4].
• Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma [4].
• Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane [6].
• We show that in zebrafish embryonic cells, Wnt11 locally functions at the plasma membrane by accumulating its receptor, Frizzled 7, on adjacent sites of cell contacts [6].

Biological context of FZD7

• The FZD1 and FZD7 genes have been mapped to human chromosome 7q21 and 2q33, respectively [7].
• Upregulation of FZD7 was associated with reduced phosphorylation of beta-catenin and led to nuclear accumulation in HCC tumors [8].
• The morphological and phenotype changes induced by FZD7 ectodomain expression in SK-CO-1 cells is thus consistent with the cells undergoing an epithelial-to-mesenchymal-like transition [2].
• Nucleotide position 153000-152216 of AC136379.2 genome sequence was identified as the evolutionarily conserved promoter region of rat Fzd7 gene, and nucleotide position 2273-3046 of AC069148.6 genome sequence as the evolutionarily conserved promoter region of human FZD7 gene [9].
• As over-expression of Frizzled-7 leads to activation of the WNT-beta-catenin-TCF pathway, up-regulation of FZD7 in human gastric cancer might play key roles in carcinogenesis through activation of the WNT-beta-catenin-TCF pathway [5].

Anatomical context of FZD7

• The level of FZD7 mRNAs 5.0 and 4.0 kb in size was high in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta [7].
• FZD7 was expressed throughout normal gastrointestinal tract, from esophagus to rectum [5].

Associations of FZD7 with chemical compounds

• FZD1, FZD2, and FZD7 share a common structure consisting of seven transmembrane domains, a cysteine-rich domain in the N-terminal extracellular region, and the C-terminal Ser/Thr-Xxx-Val motif [7].

Regulatory relationships of FZD7

• Finally, coexpression of FzE3 with Lef-1 transcription factor enhanced beta-catenin translocation to the nucleus [10].
• These observations suggest that FzE3 gene expression may down-regulate APC function and enhance beta-catenin mediated signals in poorly differentiated human esophageal carcinomas [10].

Other interactions of FZD7

• FZD5 gene, consisting of two exons, was mapped to human chromosome 2q33.3-q34 region, near the FZD7 gene and the FRA2I fragile site [11].
• We propose that Wnt11, by interacting with Frizzled 7 and Flamingo, modulates local cell contact persistence to coordinate cell movements during gastrulation [6].
• Interaction of Frizzled 7 and Dishevelled in Xenopus [12].
• A subset of those genes (wnt2b, wnt5b, wnt10b, fzd6, fzd7) showed altered expression in hDFs exposed to DBP for 3 days. wnt and fzd gene expression was not altered before hDFs contacted the DBP within the collagen sponge [13].

Analytical, diagnostic and therapeutic context of FZD7

• Furthermore, initiation of tumor formation in a xenograft tumor growth assay was attenuated in the FZD7 ectodomain expressing cells [2].

References