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A systems biology analysis of metastatic melanoma using in‐depth three‐dimensional protein profiling
Author(s) -
Han MeeJung,
Wang Huan,
Beer Lynn A.,
Tang HsinYao,
Herlyn Meenhard,
Speicher David W.
Publication year - 2010
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.200900549
Subject(s) - proteome , biology , melanoma , carcinogenesis , tumor progression , metastasis , cancer research , proteomics , suppressor , cancer , computational biology , gene , bioinformatics , genetics
Melanoma is an excellent model to study molecular mechanisms of tumor progression because melanoma usually develops through a series of architecturally and phenotypically distinct stages that are progressively more aggressive, culminating in highly metastatic cells. In this study, we used an in‐depth, 3‐D protein level, comparative proteome analysis of two genetically, very closely related melanoma cell lines with low‐ and high‐metastatic potentials to identify proteins and key pathways involved in tumor progression. This proteome comparison utilized fluorescent tagging of cell lysates followed by microscale solution IEF prefractionation and subsequent analysis of each fraction on narrow‐range 2‐D gels. LC‐MS/MS analysis of gel spots exhibiting significant abundance changes identified 110 unique proteins. The majority of observed abundance changes closely correlate with biological processes central to cancer progression, such as cell death and growth and tumorigenesis. In addition, the vast majority of protein changes mapped to six cellular networks, which included known oncogenes (JNK, c‐myc , and N‐myc ) and tumor suppressor genes (p53 and transforming growth factor‐β) as critical components. These six networks showed substantial connectivity, and most of the major biological functions associated with these pathways are involved in tumor progression. These results provide novel insights into cellular pathways implicated in melanoma metastasis.