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Global profiling of proteolytically modified proteins in human metastatic hepatocellular carcinoma cell lines reveals CAPN 2 centered network
Author(s) -
Shen Chengpin,
Yu Yanyan,
Li Hong,
Yan Guoquan,
Liu Mingqi,
Shen Huali,
Yang Pengyuan
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201200027
Subject(s) - proteolysis , cell culture , biology , metastasis , protease , hepatocellular carcinoma , cell , cell cycle , cleavage (geology) , apoptosis , secretion , microbiology and biotechnology , chemistry , biochemistry , cancer research , cancer , enzyme , genetics , paleontology , fracture (geology)
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, MHCC 97 L , and HCCLM 6, 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 CAPN 2 centered subnetwork, including SPTBN 1, ATP 5 B , and VIM , was more active in highly metastatic HCC cell line. Interestingly, proteolytic modifications of CD 44 and FN 1 were found to affect their secretion. This work suggests that proteolysis plays an important role in human HCC metastasis.