Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation.

Abstract

The majority of poorly differentiated hepatocellular carcinomas (HCCs) develop from well-differentiated tumors. Endocytosis is a cellular function which is likely to take part in this development due to its important role in regulating the abundances of vital signaling receptors. Here, we aimed to investigate the abundance of endocytosis-associated proteins in HCCs with various differentiation grades. Therefore, we analyzed 36 tissue specimens from HCC patients via LC-MS/MS-based label-free quantitative proteomics including 19 HCC tissue samples with different degrees of histological grades and corresponding non-tumorous tissue controls. As a result, 277 proteins were differentially regulated between well-differentiated tumors and controls. In moderately and poorly differentiated tumors, 278 and 1181 proteins, respectively, were significantly differentially regulated compared to non-tumorous tissue. We explored the regulated proteins based on their functions and identified thirty endocytosis-associated proteins, mostly overexpressed in poorly differentiated tumors. These included proteins that have been shown to be up-regulated in HCC like clathrin heavy chain-1 (CLTC) as well as unknown proteins, such as secretory carrier-associated membrane protein 3 (SCAMP3). The abundances of SCAMP3 and CLTC were immunohistochemically examined in tissue sections of 84 HCC patients. We demonstrate the novel association of several endocytosis-associated proteins, in particular, SCAMP3 with HCC progression.

• Authors: Wael Naboulsi, Thilo Bracht, Dominik A Megger, Henning Reis, Maike Ahrens, Michael Turewicz, Martin Eisenacher, Stephanie Tautges, Ali E Canbay, Helmut E Meyer, Frank Weber, Hideo A Baba, Barbara Sitek
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1864 Issue 11 Pg. 1579-85 (11 2016) ISSN: 0006-3002 [Print] Netherlands
• PMID: 27519163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• CLTC protein, human
• Carrier Proteins
• Membrane Proteins
• Proteome
• SCAMP3 protein, human
• Clathrin Heavy Chains

Topics

• Adult
• Aged
• Carcinoma, Hepatocellular (genetics, metabolism, pathology, surgery)
• Carrier Proteins (genetics, metabolism)
• Chromatography, Liquid
• Clathrin Heavy Chains (genetics, metabolism)
• Disease Progression
• Endocytosis (genetics)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, metabolism, pathology, surgery)
• Male
• Membrane Proteins (genetics, metabolism)
• Middle Aged
• Neoplasm Grading
• Proteome (genetics, metabolism)
• Tandem Mass Spectrometry