SFEBES2022 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)
Promotion of thyroid cancer cell migration and invasion by the proto-oncogene PBF is mediated by FGD1 and N-WASP
Selvambigai Manivannan , Mohammed Alshahrani , Caitlin EM Thornton , Saroop Raja , Merve Kocbiyik , Ling Zha , Katie Brookes , Hannah R Nieto , Martin L Read , Christopher J McCabe & Vicki E Smith
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom
Thyroid tumor progression is dependent on cell motility, a highly complex process that involves the co-ordination of cell adhesion, actin dynamics and signal transduction. The proto-oncogene pituitary tumor-transforming gene (PTTG)-binding factor (PBF/PTTG1IP) is a transmembrane glycoprotein that is overexpressed in thyroid cancer and associated with a poorer prognosis. PBF significantly promotes thyroid cancer cell migration and invasion through phosphorylation at PBF-Y174 by Src kinase. The aim of this study was to identify downstream mediators of PBF-induced thyroid cancer cell motility. A phosphoproteomic screen was performed in normal thyroid epithelial cells (Nthy-ori 3-1) with and without stable PBF overexpression. Alterations in the phosphoproteome following PBF overexpression in Nthy-ori 3-1 cells revealed an enrichment of proteins involved in cytoskeletal arrangement, cell adhesion and small GTPase activity. The phosphorylation of FGD1 (FYVE, RhoGEF and PH domain-containing protein 1) and N-WASP (Neural Wiskott-Aldrich syndrome protein) was significantly altered with PBF upregulation. Given their involvement in small GTPase signaling and cell motility we investigated a role for FGD1 and N-WASP in PBF-induced motility of TPC-1 thyroid cancer cells by scratch wound migration and Transwell invasion assays. Notably, siRNA-mediated knockdown of either FGD1 or N-WASP significantly abrogated both PBF-induced cell migration and invasion. Co-expression of either FGD1 or N-WASP with PBF did not further stimulate cell invasion. However, PBF and N-WASP acted additively to induce cell migration. Taken together, our data suggest that both FGD1 and N-WASP mediate the induction of cell motility by PBF in thyroid cancer cells, revealing novel signaling events in thyroid tumor progression.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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