ISSN: 1449-2288International Journal of Biological Sciences
Global reach, higher impact
Int J Biol Sci 2024; 20(5):1652-1668. doi:10.7150/ijbs.92988 This issue Cite
Review
The Burgeoning Significance of Liquid-Liquid Phase Separation in the Pathogenesis and Therapeutics of Cancers
1. Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha 410011, China.
2. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410078, China.
3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410078, China.
4. Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
5. Hunan key laboratory of the research and development of novel pharmaceutical preparations, Changsha Medical University, Changsha 410219, China.
* These authors contributed equally to this work.
Abstract
Liquid-liquid phase separation (LLPS) is a physiological phenomenon that parallels the mixing of oil and water, giving rise to compartments with diverse physical properties. Biomolecular condensates, arising from LLPS, serve as critical regulators of gene expression and control, with a particular significance in the context of malignant tumors. Recent investigations have unveiled the intimate connection between LLPS and cancer, a nexus that profoundly impacts various facets of cancer progression, including DNA repair, transcriptional regulation, oncogene expression, and the formation of critical membraneless organelles within the cancer microenvironment. This review provides a comprehensive account of the evolution of LLPS from the molecular to the pathological level. We explore the mechanisms by through which biomolecular condensates govern diverse cellular physiological processes, encompassing gene expression, transcriptional control, signal transduction, and responses to environmental stressors. Furthermore, we concentrate on potential therapeutic targets and the development of small-molecule inhibitors associated with LLPS in prevalent clinical malignancies. Understanding the role of LLPS and its interplay within the tumor milieu holds promise for enhancing cancer treatment strategies, particularly in overcoming drug resistance challenges. These insights offer innovative perspectives and support for advancing cancer therapy.
Keywords: liquid-liquid phase separation, biomolecular condensates, cancer, super enhancer, disease
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