Biomolecular Condensates and Their Links to Cancer Progression

Membraneless organelles formed by LLPS, termed biomolecular condensates, are increasingly recognized to play important roles in cancer emergence and progression. Cancer-related biomolecular condensates can serve in cancer progression in many ways, ranging from being platforms for proliferative signaling to hubs for enhancer element-mediated transcription of cancer genes. Therapeutics that target specific components or biophysical properties of biomolecular condensates are a fruitful avenue for future cancer diagnostics and therapy. Liquid–liquid phase separation (LLPS) has emerged in recent years as an important physicochemical process for organizing diverse processes within cells via the formation of membraneless organelles termed biomolecular condensates. Emerging evidence now suggests that the formation and regulation of biomolecular condensates are also intricately linked to cancer formation and progression. We review the most recent literature linking the existence and/or dissolution of biomolecular condensates to different hallmarks of cancer formation and progression. We then discuss the opportunities that this condensate perspective provides for cancer research and the development of novel therapeutic approaches, including the perturbation of condensates by small-molecule inhibitors. Liquid–liquid phase separation (LLPS) has emerged in recent years as an important physicochemical process for organizing diverse processes within cells via the formation of membraneless organelles termed biomolecular condensates. Emerging evidence now suggests that the formation and regulation of biomolecular condensates are also intricately linked to cancer formation and progression. We review the most recent literature linking the existence and/or dissolution of biomolecular condensates to different hallmarks of cancer formation and progression. We then discuss the opportunities that this condensate perspective provides for cancer research and the development of novel therapeutic approaches, including the perturbation of condensates by small-molecule inhibitors. a cellular mechanism to lengthen telomeres without using telomerase, most commonly seen in sarcomas, ALT differs from the telomerase-based mechanism, that uses an RNA template, because ALT uses DNA templates from existing telomeres and involves nuclear MLOs such as ALT-associated PML bodies. a controlled process inside an organism that mediates the elimination of unwanted cells; it plays important roles in organ development, and also protects against cancer formation. cellular structures formed by LLPS that perform distinct functions in cell. They are usually not enclosed by lipid bilayers. the number of times a normal human cell can divide before it stops dividing. This concept was proposed by American anatomist Leonard Hayflick in 1961 and was later found to be caused by progressive shortening of telomeres at the end of chromosomes after each round of cell division. the process by which proteins or nucleic acids demix from the milieu to form a concentrated phase, mediated by weak multivalent interactions. organelles in cell that are not surrounded by lipid bilayers. MLOs are present in both the nucleus and the cytoplasm, and many are formed by LLPS. a type of MLO that is located in the interchromosomal region inside the nucleus. Speckles contain proteins for pre-mRNA processing and their main role is in mRNA splicing. a spherical membraneless structure in the nucleus that contains proteins and DNA templates for transcribing rRNA for ribosome assembly; the nucleolus contains different subdomains for sequential rRNA synthesis. a type of perinuclear RNA granule found in the Caenorhabditis elegans embryonic cell lineage that defines the cells that make up the germline. P granules are MLOs and consist of two classes of RNA-binding proteins: the RGG-domain proteins and DEAD-box proteins. spherical MLOs in the nucleus that occupy interchromosomal space. They perform diverse functions such as ALT and DNA damage response. a monomeric guanine nucleotide-binding protein that is usually activated by receptor tyrosine kinases. RAS becomes active when bound to GTP and inactive when bound to GDP; when active, RAS triggers the activation of downstream kinases by phosphorylation. kinase-linked receptors that are usually localized on the plasma membrane; they consist of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain, and ligand binding to the receptor causes dimerization of two RTKs and cross-phosphorylation, leading to activation of downstream signaling proteins. a type of MLO formed under stress conditions that functions by sequestering mRNA transcripts, RNA-binding proteins, and translation machinery to prevent their destruction during stress. SGs usually contains Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1).