Abstract 3787: EphrinB1 is a novel microtubule associated protein whose expression may predict sensitivity to taxane

Abstract

Abstract Mitosis is a complex sequence of highly regulated events that ensures the proper segregation of sister chromatids into daughter cells. At the heart of the mitotic machinery lie the microtubules. Microtubules (MTs) are components of the cytoskeleton made up of polymerized alpha and beta tubulin dimers. MT structure and function must be maintained throughout the cell cycle to ensure proper execution of mitosis and cellular homeostasis. It has previously been reported that the protein tyrosine phosphatase, PTPN13, localizes at centrosomes from interphase, through metaphase and dramatically shifts to the spindle midzone during anaphase. During telophase, PTPN13 accumulates at the midzone, becoming concentrated at the center of the midbody during cytokinesis. We have previously demonstrated that the HPV16 E6 oncoprotein binds PTPN13 and leads to its degradation. Given PTPN13's localization to distinct compartments during mitosis/cytokinesis, we speculated that HPV infection may affect the process of mitosis. In addition, the newly appreciated roles of the PTPN13 phosphatase substrate, EphrinB1, in oncogenesis, further prompted us to define its role in mitosis. Here we report that EphrinB1 co-localizes with MTs during all phases of the cell cycle. Specifically, unphosphorylated EphrinB1 directly binds tubulin, while its phosphorylated form lacks MT binding. These characteristics are hallmarks of microtubule associated proteins (MAPs) and suggest that EphrinB1 is a novel MAP. Importantly, we demonstrate that expression of PTPN13 correlates with sensitivity to taxanes while its absence may confer resistance. In addition, we show that EphrinB1 expression affects taxane response in vitro and in vivo. We speculate that this reflects PTPN13's modulation of EphrinB1 phosphorylation and suggest that EphrinB1 is an important contributor to taxane sensitivity/resistance phenotypes in epithelial cancers. HPV infection or functional mutations of PTPN13 in non-viral cancers may predict taxane sensitivity. Note: This abstract was not presented at the meeting. Citation Format: Paola D. Vermeer, Paul L. Colbert, Daniel W. Vermeer, Bryant G. Wieking, John H. Lee. EphrinB1 is a novel microtubule associated protein whose expression may predict sensitivity to taxane. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3787. doi:10.1158/1538-7445.AM2015-3787