Abstract
Frizzled (FZD) proteins, a family of Wnt receptors, are involved in carcinogenesis in different organs. One interesting FZD protein is FZD-10 highly expressed in embryogenesis but completely absent in the membrane or cytosol of healthy proliferated cells. We studied in detail the expression level and the location of Frizzled-10 protein in different cancerous tissues, such as colon, melanoma and gastric cancer and in function of different staging of the tumor and in metastases. We observed a correlation between cancer evolution and FZD-10 expression, and localization of protein during carcinogenesis. In colon, we have an increase of cytoplasmic FZD-10 expression from hyperplastic mucosa to metastatic tissues, while the amount in the nucleus decreases significantly in T3 and T4 staging tumors as well as in metastases. In melanoma and gastric cancer, we observed the opposite trend of FZD-10 protein in the cytosol but both show a decrease in the T3 and T4 stage of the tumor and in metastases. However, the decrease is less prominent in gastric cancer.Our findings indicate an important role of FZD-10 in tumor progression especially in the later stages of tumor. The nuclear expression of FZD-10 or its absence can give a new tool for tumor staging to pathologists. For target therapy, at least for colon cancer, the high presence of FZD-10 in the later stages of tumor progression and the absence in healthy tissue present a promising new approach.
Highlights
The Wnt signaling pathway is an evolutionarily conserved pathway, which regulates cell processes such as cell migration, cell polarity, neural patterning and organogenesis during embryonic development [1]
We studied in detail the expression level and the location of Frizzled-10 protein in different cancerous tissues, such as colon, melanoma and gastric cancer and in function of different staging of the tumor and in metastases
In melanoma and gastric cancer, we observed the opposite trend of FZD-10 protein in the cytosol but both show a decrease in the T3 and T4 stage of the tumor and in metastases
Summary
The Wnt signaling pathway is an evolutionarily conserved pathway, which regulates cell processes such as cell migration, cell polarity, neural patterning and organogenesis during embryonic development [1]. Dysregulation of Wnt signaling has adverse consequences on the developing embryo. It was identified as an incident factor for some pleiotropic human pathologies, such as colon, skin, breast and glia cancers, skeletal defects and human birth defect like spina bifida [2]. Wnt binds to the N-terminal extracellular domain rich in cysteine of the Frizzled (FZD) protein receptor [3]. The 10 FZD proteins are seven-transmembrane-span protein with topological homology to G-protein coupled receptors. It interacts with co-receptor proteins or other cytoplasmic proteins like low-density-lipoprotein-related protein 5/6 (LRP5/6) and dishevelled phosphoprotein
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