Abstract
BackgroundDespite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC.MethodsThe expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown.ResultsPA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors.ConclusionsThese results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0309-z) contains supplementary material, which is available to authorized users.
Highlights
Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality
PA28α expression pattern in clinical cohort Our previously study with a small cohort indicated the potential importance of PA28α upregulation in OSCC [13, 14]
Our findings was supported by the Oncomine data analysis of two different reports [15, 16], which showed that the amount of PA28α mRNA in oral cancer tissues was significantly higher than normal tissues (Fig. 1a)
Summary
Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC. Oral squamous cell carcinoma (OSCC) represents a major subset of head and neck cancer, which is the sixth most common cancer worldwide [1]. Despite recent advances in diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality [2, 3]. Proteasomal degradation is critically dependent on proteasome activators, which bind to the end of the 20S core particle (CP) for reposition of its gating residues and allow access to doomed substrates [4]. The 11S activators are a family of small proteins that form heptameric rings and enhance peptide degradation upon binding to 20S CPs without ATP. Most recent study showed that PA28γ is critical for skin
Sign-in/Register to view highlights & summary 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 callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: 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.
