Phase separation-mediated biomolecular condensates and their relationship to tumor

Abstract

Phase separation is a cellular phenomenon where macromolecules aggregate or segregate, giving rise to biomolecular condensates resembling "droplets" and forming distinct, membrane-free compartments. This process is pervasive in biological cells, contributing to various essential cellular functions. However, when phase separation goes awry, leading to abnormal molecular aggregation, it can become a driving factor in the development of diseases, including tumor. Recent investigations have unveiled the intricate connection between dysregulated phase separation and tumor pathogenesis, highlighting its potential as a novel therapeutic target. This article provides an overview of recent phase separation research, with a particular emphasis on its role in tumor, its therapeutic implications, and outlines avenues for further exploration in this intriguing field.

Keywords: Biomolecular condensates; Phase separation; Therapeutic targets; Tumor.

Fig. 1

Formation and regulatory mechanisms of biomolecular condensates. RNA, transcribed from DNA, transits the nuclear pores to enter the cytoplasm, where it undergoes translation into proteins possessing either IDRs or multiple modular domains with analogous functions within the nucleus. Proteins with IDRs can form condensates with target proteins in the cytoplasm or, upon entering the nucleus through nuclear pores, participate in the formation of condensates with specific DNA and RNA. Conversely, proteins with specific modules assemble condensates in the cytoplasm through interaction forces between these modules. The endoplasmic reticulum and the cell membrane contribute to the creation of surface protein condensates, such as protein granules and clusters, through interaction forces on the membrane surface. The intricacies of aggregation and disaggregation of protein condensates, protein granules, and protein clusters with IDRs in the cytoplasm are finely regulated by PTMs and molecular chaperones

Fig. 2

Biomolecular condensates in tumor. Within the cellular milieu of tumors, an array of biomolecular condensates manifests. In the nucleus, these encompass SGs, FOs, PML bodies, protein condensates associated with DSBs formed by P53 and 53BP1, along with TFs, co-activators, and SEs-related transcriptional condensates. In the cytoplasm, condensates are constituted by P53 and the P53 family proteins, FOs, autophagosomes, and Iron death-related condensates formed by icFSP1 and FSP1. The presence and dynamics of these condensates significantly influence tumor proliferation, metastasis, and the development of treatment resistance