title: A physical mechanism of cancer heterogeneity.
abstract: We studied a core cancer gene regulatory network motif to uncover possible source of cancer heterogeneity from epigenetic sources. When the time scale of the protein regulation to the gene is faster compared to the protein synthesis and degradation (adiabatic regime), normal state, cancer state and an intermediate premalignant state emerge. Due to the epigenetics such as DNA methylation and histone remodification, the time scale of the protein regulation to the gene can be slower or comparable to the protein synthesis and degradation (non-adiabatic regime). In this case, many more states emerge as possible phenotype alternations. This gives the origin of the heterogeneity. The cancer heterogeneity is reflected from the emergence of more phenotypic states, larger protein concentration fluctuations, wider kinetic distributions and multiplicity of kinetic paths from normal to cancer state, higher energy cost per gene switching, and weaker stability.
authors: Physics Department, Stony Brook University, NY 11794.
authors: Cong
authors: C
authors: Chen
authors: Physics Department, Stony Brook University, NY 11794.|Chemistry Department, Stony Brook University, NY 11794.|State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022.
authors: Jin
authors: J
authors: Wang
mesh_terms: D019175:DNA Methylation; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D053263:Gene Regulatory Networks; D006657:Histones / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D006657:Histones