Nuclear microenvironment in cancer: Control through liquid-liquid phase separation

Area of Science:

• Cell Biology
• Biophysics
• Cancer Biology

Background:

• The eukaryotic nucleus contains diverse membraneless structures (e.g., nucleoli, PML bodies) that create specific microenvironments.
• Altered nuclear structures are observed in cancers, contributing to nuclear atypia, but their underlying mechanisms are unclear.

Purpose of the Study:

• To review the biophysical principles of liquid-liquid phase separation (LLPS) governing nuclear biomolecular condensate assembly.
• To explore the role of LLPS in nuclear microenvironment formation and its implications in cancer.

Main Methods:

• Review of emerging biophysical principles of LLPS in the nucleus.
• Discussion of LLPS drivers, including protein-nucleic acid interactions and intrinsically disordered regions.
• Analysis of the link between altered LLPS, nuclear events, epigenetics, and tumorigenesis.

Main Results:

• LLPS is a key biophysical mechanism driving the formation of nuclear membraneless structures.
• LLPS is typically driven by multivalent interactions and facilitated by non-coding RNAs.
• Altered LLPS is implicated in epigenetic dysregulation, cancer development, and progression.

Conclusions:

• LLPS provides a framework for understanding nuclear microenvironments and their role in biological processes.
• Dysregulation of LLPS is a significant factor in tumorigenesis and cancer progression.
• Targeting LLPS presents a potential novel therapeutic strategy for cancer intervention.