Abstract
Abstract S-phase kinase protein 2 (SKP2), is an F-box protein with proteasomal properties and has been found to be overexpressed in a variety of cancers. However its role in papillary thyroid cancer (PTC) has not been elucidated. Therefore, inactivation of SKP2 could be a viable strategy for the treatment of PTC. In the present study, we investigated the role of SKP2 and its ubiquitin-proteasome pathway in PTC using a tissue microarray cohort of 1022 PTC samples, PTC cell lines and Nude mouse model. Our immunohistochemistry data showed that SKP2 was over-expressed in 75.1% of PTC cases and was clinically, significantly associated with extra thyroidal extension (p=0.0331), Tall cell variant (p=0.0070), and presence in surgical margins (p=0.0347). Bortezomib as well as SKP2 specific siRNA caused downregulation of SKP2 leading to dose-dependent growth inhibition and induction of apoptosis via mitochondrial apoptotic pathway in PTC cell lines. Furthermore, we found that treatment of PTC cells with Bortezomib caused up-regulation of DR5 via generation of reactive oxygen species (ROS). Finally, Bortezomib treatment augmented TRAIL mediated anti-cancer effect on PTC xenograft tumor growth in nude mice. These data suggest that Bortezomib is a viable therapeutic option for the treatment of PTC either alone or in combination with other apoptotic agents such as TRAIL. Note: This abstract was not presented at the meeting. Citation Format: Pratheeshkumar Poyil, Rong Bu, Abdul K. Siraj, Sandeep Kumar P, Khawla S. Al-Kuraya. Inhibition of papillary thyroid cancer cells progression by targeting skp2 via ros-erk-chop-dr5 pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1329. doi:10.1158/1538-7445.AM2017-1329
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
