Liquid-liquid phase separation in tumor biology

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.

Automated summary

Liquid-liquid phase separation (LLPS) is a novel principle that explains the precise regulation of spatial and temporal organization in living cells. It plays a crucial role in various cellular processes and its dysregulation has been linked to cancer development. This review comprehensively summarizes the mechanisms of biomolecular condensate formation and function, and discusses recent advances in understanding the role of aberrant LLPS in cancer pathology. Furthermore, the therapeutic potential of targeting LLPS in cancer research and development of drug candidates is also discussed.