critical role of vcpp97 in the pathogenesis and progression of non-small cell lung carcinomavcpp97关键作用的非小细胞肺癌的发病和进展.pdfVIP

Critical Role of VCP/p97 in the Pathogenesis and Progression of Non-Small Cell Lung Carcinoma 2 2 2 2 4 2 Christopher W. Valle , Taehong Min , Manish Bodas , Steven Mazur , Shahnaz Begum , Danni Tang , Neeraj Vij1,2,3* 1Johns Hopkins Physical Sciences in Oncology Center, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Pediatric Respiratory Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, 3 Institute of NanoBiotechnology, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, 4 Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America Abstract Background: Valosin-containing protein (VCP)/p97 is an AAA ATPase molecular chaperone that regulates vital cellular functions and protein-processing. A recent study indicated that VCP expression levels are correlated with prognosis and progression of non-small cell lung carcinoma (NSCLC). We not only verified these findings but also identified the specific role of VCP in NSCLC pathogenesis and progression. Methodology/Principal Findings: Our results show that VCP is significantly overexpressed in non-small cell lung carcinoma (NSCLC) as compared to normal tissues and cell lines (p,0.001). Moreover, we observed the corresponding accumulation of ubiquitinated-proteins in NSCLC cell lines and tissues as compared to the normal controls. VCP inhibition by si/shRNA or small-molecule (Eeyarestatin I, EerI) significantly (p,0.05, p,0.00007) suppressed H1299 proliferation and migration but induced (p,0.00001) apoptosis. Cell cycle analysis by flow cytometry verified this data and shows th