title: Global profiling of proteolytically modified proteins in human metastatic hepatocellular carcinoma cell lines reveals CAPN2 centered network.
abstract: Proteolysis affects every protein at some point in its life cycle. Many biomarkers of disease or cancer are stable proteolytic fragments in biological fluids. There is great interest and a challenge in proteolytically modified protein study to identify physiologic protease-substrate relationships and find potential biomarkers. In this study, two human hepatocellular carcinoma (HCC) cell lines with different metastasis potential, MHCC97L, and HCCLM6, were researched with a high-throughput and sensitive PROTOMAP platform. In total 391 proteins were found to be proteolytically processed and many of them were cleaved into persistent fragments instead of completely degraded. Fragments related to 161 proteins had different expressions in these two cell lines. Through analyzing these significantly changed fragments with bio-informatic tools, several bio-functions such as tumor cell migration and anti-apoptosis were enriched. A proteolysis network was also built up, of which the CAPN2 centered subnetwork, including SPTBN1, ATP5B, and VIM, was more active in highly metastatic HCC cell line. Interestingly, proteolytic modifications of CD44 and FN1 were found to affect their secretion. This work suggests that proteolysis plays an important role in human HCC metastasis.
authors.affiliation: Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, P. R. China.
authors.forename: Chengpin
authors.initials: C
authors.lastname: Shen
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Guoquan
authors.initials: G
authors.lastname: Yan
authors.forename: Mingqi
authors.initials: M
authors.lastname: Liu
authors.forename: Huali
authors.initials: H
authors.lastname: Shen
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D002154:Calpain / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry* / Q000378:metabolism*; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D060066:Protein Interaction Maps; D059748:Proteolysis; D020543:Proteome / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D020543:Proteome; D002154:Calpain; C569870:CAPN2 protein, human