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CORRELATION OF ACTIVATED PROTEIN WNT-5A WITH INVASIVE MIGRATION OF BREAST CANCER CELLS.

Gan Sze Hui .. Context: Growing evidence demonstrates that protein Wnt-5A is associated with MMP9 activity in the breast carcinoma and its invasive migration. However, little is known or unclearly known about the relation between the suppressive signaling pathway of protein Wnt-5A in normal healthy women and patient with breast carcinoma of different molecular classification groups in order to evaluate the mortality and prognosis in each particular group as well.

Protein Wingless-type MMTV integration site family, member 5A (WNT-5A) is a protein that in humans is encoded by the WNT5A gene family of secreted glycoproteins with a conserved pattern of cysteine residues (2224) which consists of structurally related genes that encode secreted signaling proteins to inhibit migration and metastasis of a variety of cancer cell such as in breast carcinoma. Thus, in those patients with primary breast cancer in which WNT-5A was expressed have a better prognosis. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. The WNT5A is highly expressed in the dermal papilla of depilated skin. It encodes a protein showing 98%, 98%, and 87% amino acid identity to the Wnt5A protein of mouse, rat and the Xenopus, respectively. Wnt proteins are subdivided into two functional classes on the basis of their different biological effects. Members of the Wnt1/Wingless class transform C57MG cells in embryos of Xenopus Laevis which proves that human frizzled-5 (hFz5) is the receptor for the Wnt5A ligand and the Wnt5A/hFz5 signaling mediates secondary axis induction. This effect is based on activation of the Wnt-catenin pathway, which involves the stabilization of cytoplasmic -catenin and transcriptional regulation through the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors. Members of the Wnt5A class fail in both assays and activate non-canonical Wnt pathways. These involve different kinases such as protein kinase C (PKC), calmodulin-dependent protein kinase II (CamKII) and c-Jun N terminal kinase (JNK), as well as phosphatases such as calcineurin (CaCN). Members of the Rho class of GTPases such as Rho, Rac and Cdc42 are regulated by non-canonical Wnt signaling as well. This pathway resembles the planar cell polarity pathway in Drosophila. Non-canonical Wnt pathways inhibit the canonical Wnt-catenin pathway.

The specificity of Wnt signaling depends on the interaction of Wnts with its receptors of the Frizzled and low-density lipoprotein receptor-related protein (LRP) families as well as co receptors of the Ror and Ryk families. Wnt5A has been shown to regulate cell movements during gastrulation in fish and frogs. Wnt5A has also some influence on dorsoventral patterning as shown in fish that are mutant for Wnt5A. Furthermore, Wnt5A has been implicated as a tumor suppressor gene. Additionally, a role for Wnt5A in metastasis has been reported. Treatment of primary midbrain precursor cells with purified Wnt5A induced differentiation into dopaminergic, tyrosine hydroxylase-positive neurons.



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