title: Proliferation and tissue remodeling in cancer: the hallmarks revisited.
abstract: Although cancers are highly heterogeneous at the genomic level, they can manifest common patterns of gene expression. Here, we use gene expression signatures to interrogate two major processes in cancer, proliferation and tissue remodeling. We demonstrate that proliferation and remodeling signatures are partially independent and result in four distinctive cancer subtypes. Cancers with the proliferation signature are characterized by signatures of p53 and PTEN inactivation and concomitant Myc activation. In contrast, remodeling correlates with RAS, HIF-1α and NFκB activation. From the metabolic point of view, proliferation is associated with upregulation of glycolysis and serine/glycine metabolism, whereas remodeling is characterized by a downregulation of oxidative phosphorylation. Notably, the proliferation signature correlates with poor outcome in lung, prostate, breast and brain cancer, whereas remodeling increases mortality rates in colorectal and ovarian cancer.
authors.affiliation: The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Markert
authors.forename: A J
authors.initials: AJ
authors.lastname: Levine
authors.forename: A
authors.initials: A
authors.lastname: Vazquez
mesh_terms: D049109:Cell Proliferation; D016000:Cluster Analysis; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010085:Oxidative Phosphorylation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D018631:ras Proteins