Journal
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
Volume 117, Issue 1, Pages 30-42Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2015.01.004
Keywords
Prostate Cancer; Endogenous Molecular-cellular Network; Dynamical System; Potential Landscape; Attractors
Categories
Funding
- National 973 Project [2010CB529200]
- Natural Science Foundation of China [NSFC91029738]
- State Key Laboratory of Oncogenes and Related Genes [90-10-11]
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We explored endogenous molecular-cellular network hypothesis for prostate cancer by constructing relevant endogenous interaction network model and analyzing its dynamical properties. Molecular regulations involved in cell proliferation, apoptosis, differentiation and metabolism are included in a hierarchical mathematical modeling scheme. This dynamical network organizes into multiple robust functional states, including physiological and pathological ones. Some states have characteristics of cancer: elevated metabolic and immune activities, high concentration of growth factors and different proliferative, apoptotic and adhesive behaviors. The molecular profile of calculated cancer state agrees with existing experiments. The modeling results have additional predictions which may be validated by further experiment: 1) Prostate supports both stem cell like and liver style proliferation; 2) While prostate supports multiple cell types, including basal, luminal and endocrine cell type differentiated from its stem cell, luminal cell is most likely to be transformed malignantly into androgen independent type cancer; 3) Retinoic acid pathway and C/EBP alpha are possible therapeutic targets. (C) 2015 Elsevier Ltd. All rights reserved.
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