title: Quantitative implementation of the endogenous molecular-cellular network hypothesis in hepatocellular carcinoma.
abstract: A quantitative hypothesis for cancer genesis and progression-the endogenous molecular-cellular network hypothesis, intended to include both genetic and epigenetic causes of cancer-has been proposed recently. Using this hypothesis, here we address the molecular basis for maintaining normal liver and hepatocellular carcinoma (HCC), and the potential strategy to cure or relieve HCC. First, we elaborate the basic assumptions of the hypothesis and establish a core working network of HCC according to the hypothesis. Second, we quantify the working network by a nonlinear dynamical system. We show that the working network reproduces the main known features of normal liver and HCC at both the modular and molecular levels. Lastly, the validated working network reveals that (i) specific positive feedback loops are responsible for the maintenance of normal liver and HCC; (ii) inhibiting proliferation and inflammation-related positive feedback loops and simultaneously inducing a liver-specific positive feedback loop is predicated as a potential strategy to cure or relieve HCC; and (iii) the genesis and regression of HCC are asymmetric. In light of the characteristic properties of the nonlinear dynamical system, we demonstrate that positive feedback loops must exist as a simple and general molecular basis for the maintenance of heritable phenotypes, such as normal liver and HCC, and regulating the positive feedback loops directly or indirectly provides potential strategies to cure or relieve HCC.
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine , Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China.
authors.forename: Gaowei
authors.initials: G
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine , Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute , Shanghai Jiao Tong University School of Medicine , Shanghai 200032 , People's Republic of China.
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine , Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China ; Department of Physics , Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China ; State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute , Shanghai Jiao Tong University School of Medicine , Shanghai 200032 , People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ao
keywords: endogenous molecular–cellular network hypothesis; hepatocellular carcinoma; nonlinear dynamical system; positive feedback loop; systems biology