Feedback, crosstalk and competition: Ingredients for emergent non‐linear behaviour in the pi3k/mtor signalling network

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The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision‐making by the cell. To facilitate this, the pathway has evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neigh-bouring signalling pathways, making it a highly non‐linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed‐forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non‐linear and dynamic network behav-iours that arise from these regulations, uncovered through computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysreg-ulation in pathologies including cancer and diabetes, a coherent and systems‐level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.

Original languageEnglish
Article number6944
Number of pages14
JournalInternational Journal of Molecular Sciences
Issue number13
Publication statusPublished - 1 Jul 2021


  • Cancer
  • Crosstalk
  • Feedback loop
  • Nonlinear dynamics
  • PI3K/mTOR signalling

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