Abstract B15: Transforming growth factor {beta} type III (T{beta}RIII/Betaglycan) suppresses canonical Wnt signaling in ovarian cancer

Ovarian cancer remains the deadliest gynecologic malignancy and the fifth leading cause of death from cancer in women[1]. Transforming growth factor β Type III (TβRIII/Betaglycan) receptor is a ubiquitously expressed co-receptor for the TGF-β ligand superfamily[2] whose expression is significantly decreased or lost in human epithelial ovarian tumors compared to normal tissue, with loss of TβRIII expression correlating with tumor grade and ovarian cancer progression[3]. TβRIII has increasing roles in suppressing cancer progression via cell motility[4], cell adhesion[5], and cell differentiation[2], largely independent of its TGF-β co-receptor functions[2, 3]. Structurally, TβRIII is a transmembrane proteoglycan containing both heparan sulfate and chondroitin sulfate glycosaminoglycan (GAG) chain modifications in its extracellular domain[5] that can interact with non-TGF-β family members, namely FGF2, via its GAG chains to regulate tumorigenesis[2].There is increasing evidence that Wnt glycoproteins that play complex roles in cancer[1, 6-11] have a high affinity for GAG chains on proteoglycans[12, 13]. Thus, we have initiated studies to determine the possible role of TβRIII on canonical Wnt3a signaling in ovarian cancer. Using a combination of cell signaling and biochemical approaches in ovarian cancer models, we find that TβRIII suppresses Wnt3a signaling by binding Wnt3a via its heparan sulfated GAG chains, which leads to pert...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways: Wnt: Poster Presentations - Proffered Abstracts Source Type: research