Abstract
Although there is extensive information on gene expression and molecular interactions in various cell types, integrating those data in a functionally coherent manner remains challenging. This study explores the premise that genes whose expression at the mRNA level is correlated over diverse cell lines are likely to function together in a network of molecular interactions. We previously derived expression-correlated gene clusters from the database of the NCI-60 human tumor cell lines and associated each cluster with function categories of the Gene Ontology (GO) database. From a cluster rich in genes associated with GO categories related to cell migration, we extracted 15 genes that were highly cross-correlated; prominent among them were RRAS, AXL, ADAM9, FN14, and integrin-beta1. We then used those 15 genes as bait to identify other correlated genes in the NCI-60 database. A survey of current literature disclosed, not only that many of the expression-correlated genes engaged in molecular interactions related to migration, invasion, and metastasis, but that highly cross-correlated subsets of those genes engaged in specific cell migration processes. We assembled this information in molecular interaction maps (MIMs) that depict networks governing 3 cell migration processes: degradation of extracellular matrix, production of transient focal complexes at the leading edge of the cell, and retraction of the rear part of the cell. Also depicted are interactions controlling the release and effects of calcium ions, which may regulate migration in a spaciotemporal manner in the cell. The MIMs and associated text comprise a detailed and integrated summary of what is currently known or surmised about the role of the expression cross-correlated genes in molecular networks governing those processes.
Highlights
A great deal of information has accumulated on gene expression and molecular interactions in various cell types, relating those data to cell functions remains challenging
We recently developed a procedure that generated gene clusters based on NCI-60 gene expression profiles and that associated the gene clusters with sets of function categories defined by the Gene Ontology (GO) database [9]
In order to select a group of genes that are likely to engage in molecular interactions leading to a particular function, we began with the 83 genes that constitute cluster 52/160 of Zeeberg et al [9], derived on the basis of similarity of gene expression profile across the NCI-60 cell lines
Summary
A great deal of information has accumulated on gene expression and molecular interactions in various cell types, relating those data to cell functions remains challenging. Malignant cells often retain histological characteristics resembling the tissue of origin, and tumor cell lines derived from the same tissue of origin often retain similar gene expression patterns [1,2,3]. Groups of genes that are expressed in tumor cell lines from one or more tissues of origin may reflect some aspect of the cells’ ‘‘life-styles’’. Cell lines having epithelial versus mesenchymal characteristics, for example, have gene expression patterns that tend to correspond to those respective tissue types Mutations and genome scrambling in malignant tumors, can cause gene expression patterns to diverge substantially among different cell lines of a given tissue type
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