Protein complex, gene, and regulatory modules in cancer heterogeneity.

The recent excitement generated by the analysis of human cancer genomes is tempered by the uncovered regulatory complexity. Interactions between heterogeneous multiprotein complex and genetic and regulatory modules form networks unique not only to different tumor types, but also, surprisingly, to similar type tumors generating molecular/cellu-lar heterogeneity that ultimately control cancer cell proliferation and invasion, endowing tumors with robustness. It is, however, unknown how cancer-specific modules and their networks determine tumor behavior, or how they directly or indirectly reorganize signaling complexes into novel networks even within the same tumor, making tumor treatment problematic. Experimental and theoretical data from high-throughput studies suggest that the key lies in characterizing cancer-specific protein complex modules, identifying common nodes, that is, the key proteins (oncogenes or other molecules) shared by different complex modules and networks, and in dissecting adaptive, inter-module functional communication in the control of tumor growth by rearrangement of protein complex modules.