Emerging Implications of Phase Separation in Cancer

Abstract

In eukaryotic cells, biological activities are executed in distinct cellular compartments or organelles. Canonical organelles with membrane-bound structures are well understood. Cells also inherently contain versatile membrane-less organelles (MLOs) that feature liquid or gel-like bodies. A biophysical process termed liquid-liquid phase separation (LLPS) elucidates how MLOs form through dynamic biomolecule assembly. LLPS-related molecules often have multivalency, which is essential for low-affinity inter- or intra-molecule interactions to trigger phase separation. Accumulating evidence shows that LLPS concentrates and organizes desired molecules or segregates unneeded molecules in cells. Thus, MLOs have tunable functional specificity in response to environmental stimuli and metabolic processes. Aberrant LLPS is widely associated with several hallmarks of cancer, including sustained proliferative signaling, growth suppressor evasion, cell death resistance, telomere maintenance, DNA damage repair, etc. Insights into the molecular mechanisms of LLPS provide new insights into cancer therapeutics. Here, the current understanding of the emerging concepts of LLPS and its involvement in cancer are comprehensively reviewed.

Keywords: biomolecular condensates; cancer; novel therapeutics; phase separation.