Regulation patterns in signaling networks of cancer.
BACKGROUND
Formation of cellular malignancy results from the disruption of fine tuned signaling homeostasis for proliferation, accompanied by mal-functional signals for differentiation, cell cycle and apoptosis. We wanted to observe central signaling characteristics on a global view of malignant cells which have evolved to selfishness and independence in comparison to their non-malignant counterparts that fulfill well defined tasks in their sample.


RESULTS
We investigated the regulation of signaling networks with twenty microarray datasets from eleven different tumor types and their corresponding non-malignant tissue samples. Proteins were represented by their coding genes and regulatory distances were defined by correlating the gene-regulation between neighboring proteins in the network (high correlation = small distance). In cancer cells we observed shorter pathways, larger extension of the networks, a lower signaling frequency of central proteins and links and a higher information content of the network. Proteins of high signaling frequency were enriched with cancer mutations. These proteins showed motifs of regulatory integration in normal cells which was disrupted in tumor cells.


CONCLUSIONS
Our global analysis revealed a distinct formation of signaling-regulation in cancer cells when compared to cells of normal samples. From these cancer-specific regulation patterns novel signaling motifs are proposed.
Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Bioquant, University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
Gunnar
G
Schramm
Nandakumar
N
Kannabiran
Rainer
R
König
D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction
D011506:Proteins