Model Checking a Synchronous Diabetes-Cancer Logical Network
Edmund M. Clarke.
Cancer and diabetes are two highly malignant diseases. Accumulating evidence suggests that cancer incidence
might be associated with diabetes mellitus, especially Type-2 diabetes which is characterized by hyperinsulinemia,
hyperglycemia, obesity, and overexpression of multiple components of the WNT pathway. These diabetes risk factors can
activate a number of signaling pathways that are important in the development of different cancers. To systematically
understand the signaling components that link diabetes and cancer risk, we have constructed a single-cell, synchronous
Boolean network model by integrating the signaling pathways that are influenced by these risk factors. Then, we have
applied Model Checking, a formal verification approach, to qualitatively study several temporal logic properties of our
diabetes-cancer model. Our aim was to study insulin resistance, cancer cell proliferation and apoptosis. The verification
results show that the diabetes risk factors might not increase cancer risk in normal cells, but they will promote cell
proliferation if the cell is in a precancerous or cancerous stage characterized by losses of the tumor-suppressor proteins
ARF and INK4a.
Keywords: Apoptosis, boolean network, cancer, diabetes, model checking, signaling pathway, temporal logic, Glucose-AMPK-mTOR, Insulin-PI3K, Obesity-ROS-JNK
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