Phase separation in Cancer: From the Impacts and Mechanisms to Treatment potentials

Abstract

Cancer is a public health problem of great concern, and it is also one of the main causes of death in the world. Cancer is a disease characterized by dysregulation of diverse cellular processes, including avoiding growth inhibitory factors, avoiding immune damage and promoting metastasis, etc. However, the precise mechanism of tumorigenesis and tumor progression still needs to be further elucidated. Formations of liquid-liquid phase separation (LLPS) condensates are a common strategy for cells to achieve diverse functions, such as chromatin organization, signal transduction, DNA repair and transcriptional regulation, etc. The biomolecular aggregates formed by LLPS are mainly driven by multivalent weak interactions mediated by intrinsic disordered regions (IDRs) in proteins. In recent years, aberrant phase separations and transition have been reported to be related to the process of various diseases, such as neurodegenerative diseases and cancer. Herein, we discussed recent findings that phase separation regulates tumor-related signaling pathways and thus contributes to tumor progression. We also reviewed some tumor virus-associated proteins to regulate the development of virus-associated tumors via phase separation. Finally, we discussed some possible strategies for treating tumors by targeting phase separation.

The role of physics in multiomics and cancer evolution

“…Mechanics has a further role in cellular organisation, for example in phase separation. Phase separation is the process responsible for cellular compartmentalization, involving the assembly of condensates which are membraneless organelles such as stress granules and polycomb bodies (18). Dysregulated components in cancer can affect the location and the regulation of condensates, thereby leading to altered gene expression (19).…”

Phase separation in cancer at a glance

“…The disheveled binding antagonist of -catenin 1 (DACT1), a target gene of transforming growth factor (TGF-), can assemble BMCs within the cytoplasm that sequester casein kinase 2 (CK2) and prevent WNT signaling. Thus, DACT1 BMCs play a vital role in the metastatic process of breast and prostate cancer cells [ 33 , 34 ]. IDRs within the signalosome scaffold protein Dishevelled 2 (Dvl2) mediate LLPS.…”

Liquid-Liquid Phase Separation Promotes Protein Aggregation and Its Implications in Ferroptosis in Parkinson’s Disease Dementia

“…Because the molecules near the droplet's surface are more unstable than the molecular energy inside the droplet, when two droplets of similar size contact each other, the surface free energy is driven and will spontaneously fuse into larger droplets. This active aggregation was mediated by microtubules in stress granules (SGS), microtubules in the processing body (P-body), and motor proteins [ 32 , 33 ]. Alberti et al demonstrated through in vivo imaging and fluorescent labeling of P-body that these particles have liquid properties and can not only fuse, split, and change in size but also reversibly.…”