摘要
Liquid–liquid phase separation(LLPS)is a novel principle for explaining the precise spatial and temporal regulation in living cells.LLPS compartmentalizes proteins and nucleic acids into micron-scale,liquid-like,membraneless bodies with specific functions,which were recently termed biomolecular condensates.Biomolecular condensates are executors underlying the intracellular spatiotemporal coordination of various biological activities,including chromatin organization,genomic stability,DNA damage response and repair,transcription,and signal transduction.Dysregulation of these cellular processes is a key event in the initiation and/or evolution of cancer,and emerging evidence has linked the formation and regulation of LLPS to malignant transformations in tumor biology.In this review,we comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant LLPS.In addition,we discuss the therapeutic perspectives of LLPS in cancer research and the most recently developed drug candidates targeting LLPS modulation that can be used to combat tumorigenesis.
基金
study was jointly supported by the National Natural Science Foundation of China(U21A20374 and 82072698)
Shanghai Municipal Science and Technology Major Project(21JC1401500)
Scientific Innovation Project of Shanghai Education Committee(2019-01-07-00-07-E00057)
Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1006A)
Xuhui District Artificial Intelligence Medical Hospital Cooperation Project(2021-011).
