Inferring the Effects of Honokiol on the Notch Signaling Pathway in SW480 Colon Cancer Cells.
In a tumor cell, the development of acquired therapeutic resistance and the ability to survive in extracellular environments that differ from the primary site are the result of molecular adaptations in potentially highly plastic molecular networks. The accurate prediction of intracellular networks in a tumor remains a difficult problem in cancer informatics. In order to make truly rational patient-driven therapeutic decisions, it will be critical to develop methodologies that can accurately infer the molecular circuitry in the cells of a specific tumor. Despite enormous heterogeneity, cellular networks elicit deterministic digital-like responses. We discuss the use and limitations of methodologies that model molecular networks in cancer cells as a digital circuit. We also develop a network model of Notch signaling in colon cancer using a novel reverse engineering logic-based method and published western blot data to elucidate the interactions likely present in the circuits of the SW480 colon cancer cell line. Within this framework, we make predictions related to the role that honokiol may be playing as an anti-cancer drug.
Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan, Medical School, Ann Arbor, MI, USA. ; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. ; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA. ; Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI, USA.
Michelle L
ML
Wynn
Columbia University College of Physicians and Surgeons, New York, NY, USA.
Nikita
N
Consul
Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan, Medical School, Ann Arbor, MI, USA.
Sofia D
SD
Merajver
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. ; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA. ; Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, MI, USA.
Santiago
S
Schnell
Notch; honokiol; logic networks; reverse engineering; signaling pathways