Cell Signaling

Viewing the Cancer Landscape

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Science  23 Nov 2012:
Vol. 338, Issue 6110, pp. 1010
DOI: 10.1126/science.338.6110.1010-c

The cellular signaling pathways that control cell physiology are key targets of therapeutic strategies, like those aimed at killing cancer cells. But agents that cause DNA damage in cancer cells lead to cell death through a complicated network of pathways, including positive and negative feedback loops, that control the activity of the tumor suppressor p53. To help clarify more effective strategies to promote cell death in cancer cells, Choi et al. used a computational approach in which the potential energy landscape is mapped as a three-dimensional surface in which depressions represent stable states or “attractors.” These attractors represent alternative cell fates. With a simplified network analyzed with a Boolean network model, the authors identified key network components that together could force cells to undergo apoptosis rather than proliferation or cell cycle arrest. Experiments verified that modulation of these two components effectively promoted cell death. The approach may provide a way to address complex system-level data and models to more accurately predict ways to steer cells to adopt a desired physiological state.

CREDIT: M. CHOI ET AL., SCIENCE SIGNALING 5 (20 OCTOBER 2012)/IMAGE BY KWANG-HYUN CHO/KAIST

Sci. Signal. 5, ra83 (2012).

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