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Review
. 2023 Apr 1;21(1):237.
doi: 10.1186/s12967-023-04082-x.

Phase separation in cancer at a glance

Qingqing Xie  1 , Jiejuan Cheng  2 , Wuxuan Mei  3 , Dexing Yang  1 , Pengfei Zhang  1 , Changchun Zeng  4
Affiliations
Review

Phase separation in cancer at a glance

Qingqing Xie et al. J Transl Med. .

Abstract

Eukaryotic cells are segmented into multiple compartments or organelles within the cell that regulate distinct chemical and biological processes. Membrane-less organelles are membrane-less microscopic cellular compartments that contain protein and RNA molecules that perform a wide range of functions. Liquid-liquid phase separation (LLPS) can reveal how membrane-less organelles develop via dynamic biomolecule assembly. LLPS either segregates undesirable molecules from cells or aggregates desired ones in cells. Aberrant LLPS results in the production of abnormal biomolecular condensates (BMCs), which can cause cancer. Here, we explore the intricate mechanisms behind the formation of BMCs and its biophysical properties. Additionally, we discuss recent discoveries related to biological LLPS in tumorigenesis, including aberrant signaling and transduction, stress granule formation, evading growth arrest, and genomic instability. We also discuss the therapeutic implications of LLPS in cancer. Understanding the concept and mechanism of LLPS and its role in tumorigenesis is crucial for antitumor therapeutic strategies.

Keywords: Cancer; Cancer biology; Mechanism; Phase separation; Therapy.

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Conflict of interest statement

The authors have no conflict of interest.

Figures

Fig. 1
Fig. 1
illustrates the biological processes involved in LLPS. a The activation or suppression of genes, including transcription, epigenetics, and translation. b Processing bodies, Stress granules, and P granules are formed as membrane-less organelles. c The process of signal transduction. d Assembly of the cytoskeleton. e Degradation of proteins
Fig. 2
Fig. 2
An overview of the biological functions of LLPS-mediated membrane-less biomolecular condensates is presented, including X-chromosome inactivation/paraspeckle formation, transcription/chromatin organization, cytoplasmic DNA sensing, DNA damage response, stress granule formation, proteasome/autophagosome formation, tumorigenesis, synaptic vesicle active zone formation, and ribonucleoprotein synthesis
Fig. 3
Fig. 3
An innovative PROTAC, ARV-825, which links BRD4 to E3 ubiquitin ligase, effectively degrades BRD4 protein. ARV-825-induced BRD4 aggregation disrupts LLPS and suppresses BRD-4-dependent transcription. PROTAC proteolysis targeting chimera
Fig. 4
Fig. 4
Chloroquine inhibits autophagy by impairing the autophagosome-lysosome fusion process, thereby increasing target protein levels. LLPS regulates the assembly of autophagy substrates
See this image and copyright information in PMC

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