Research Progress in the Role of Liquid-Liquid Phase Separation in Human Cancer

TAO Ruolin, ZHANG Shuijun, GUO Wenzhi, YAN Zhiping


Liquid-liquid phase separation (LLPS) is a reversible process, during which biological macromolecules, including proteins and nucleic acids, condense into liquid membraneless organelles under the influence of weak multivalent interactions. Currently, fluorescence recovery after photobleaching is the primary method used to detect the phase separation of biological macromolecules. Recent studies have revealed the link between abnormal LLPS and the pathogenesis and development of various human cancers. Through phase separation or abnormal phase separation, tumor-related biological macromolecules, such as mRNA, long noncoding RNAs (lncRNAs), and tumor-related proteins, can affect transcriptional translation and DNA damage repair, regulate the autophagy and ferroptosis functions of cells, and thus regulate the development of various tumors. In this review, we summarized the latest research findings on the mechanism of LLPS in the pathogenesis and progression of tumors and elaborated on the promotion or inhibition of autophagy, tumor immunity, DNA damage repair, and cell ferroptosis after abnormal phase separation of biomolecules, including mRNA, lncRNA, and proteins, which subsequently affects the pathogenesis and progression of tumors. According to published findings, many biological macromolecules can regulate transcriptional translation, expression, post-transcriptional modification, cell signal transduction, and other biological processes through phase separation. Therefore, further expansion of the research field of phase separation and in-depth investigation of its molecular mechanisms and regulatory processes hold extensive research potential.

Keywords: Liquid-liquid phase separation,  Biomolecular condensates,  Cancer, Review


Full Text:



ZHANG H, JI X, LI P, et al. Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases. Sci China Life Sci,2020,63(7): 953–985. doi: 10.1007/s11427-020-1702-x.

DENG H, MIN E, BAEYENS N, et al. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling. Proc Natl Acad Sci U S A,2021,118(37): e2105339118. doi: 10.1073/pnas. 2105339118.

LI P, BANJADE S, CHENG H C, et al. Phase transitions in the assembly of multivalent signalling proteins. Nature,2012,483(7389): 336–340. doi: 10.1038/nature10879.

ALBERTI S, GLADFELTER A, MITTAG T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell,2019,176(3): 419–434. doi: 10.1016/j.cell.2018.12.035.

LARSON A G, ELNATAN D, KEENEN M M, et al. Liquid droplet formation by HP1alpha suggests a role for phase separation in heterochromatin. Nature,2017,547(7662): 236–240. doi: 10.1038/nature22822.

REN J, ZHANG Z, ZONG Z, et al. Emerging implications of phase separation in cancer. Adv Sci (Weinh),2022,9(31): e2202855. doi: 10. 1002/advs.202202855.

BOEYNAEMS S, ALBERTI S, FAWZI N L, et al. Protein phase separation: a new phase in cell biology. Trends Cell Biol,2018,28(6): 420–435. doi: 10.1016/j.tcb.2018.02.004.

ALBERTI S, DORMANN D. Liquid-liquid phase separation in disease. Annu Rev Genet,2019,53: 171–194. doi: 10.1146/annurev-genet-112618-043527.

SHIN Y, BRANGWYNNE C P. Liquid phase condensation in cell physiology and disease. Science,2017,357(6357): eaaf4382. doi: 10.1126/science.aaf4382.

MATHIEU C, PAPPU R V, PAUL TAYLOR J. Beyond aggregation, Pathological phase transitions in neurodegenerative disease. Science, 2020,370(6512): 56–60. doi: 10.1126/science.abb8032.

ZENG M, SHANG Y, ARAKI Y, et al. Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity. Cell,2016,166(5): 1163–1175.e1112. doi: 10.1016/j.cell.2016.07. 008.

GUO Q, SHI X, WANG X. RNA and liquid-liquid phase separation. Noncoding RNA Res,2021,6(2): 92–99. doi: 10.1016/j.ncrna.2021.04.003.

BANANI S F, LEE H O, HYMAN A A, et al. Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol,2017,18(5): 285–298. doi: 10.1038/nrm.2017.7.

ZEMLA J, DANILKIEWICZ J, ORZECHOWSKA B, et al. Atomic force microscopy as a tool for assessing the cellular elasticity and adhesiveness to identify cancer cells and tissues. Semin Cell Dev Biol,2018,73: 115–124. doi: 10.1016/j.semcdb.2017.06.029.

BOIJA A, KLEIN I A, YOUNG R A. Biomolecular condensates and cancer. Cancer Cell,2021,39(2): 174–192. doi: 10.1016/j.ccell.2020.12. 003.

BIRSA N, ULE A M, GARONE M G, et al. FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation. Sci Adv,2021,7(30): eabf8660. doi: 10.1126/sciadv.abf8660.


  • There are currently no refbacks.