Abstract: Cellular functions in biological systems are regulated by the underlying gene regulatory networks. Recently, a "mode-hopping" phenomenon is observed in NF-kB gene regulatory network with oscillatory tumor necrosis factor (TNF) inputs. It was shown that noise facilitates the switch between different oscillation modes. However, the underlying mechanism of this noise-induced "cellular mode-hopping" behavior remains elusive. We applied a landscape and flux approach to study the stochastic dynamics and global stability of the NF-kB regulatory system. The potential landscape of NF-kB system exhibits a "double ring valley" shape. Barrier heights from landscape topography provide quantitative measures for the global stability and transition feasibility of double oscillation system. We demonstrate that the double oscillation system is driven by both landscape and flux, which govern the dynamical "mode-hopping" behavior of the NF-kB regulatory system. Landscape attracts the system into the "double ring valley", and flux drives the system moving along the cycles. As the amplitude of TNF input increases, the flux contribution from total driving force increases, and the landscape changes from one cycle to two cycles and finally to the chaotic dynamics. This indicates that the probabilistic flux may provide an origin of chaotic behavior. Using an EMT-metastasis model as an example, I’ll also talk about a landscape control strategy in cell fate decisions.