The emerging role of receptor tyrosine kinase phase separation in cancer

Trends Cell Biol. 2024 May;34(5):371-379. doi: 10.1016/j.tcb.2023.09.002. Epub 2023 Sep 28.

Abstract

Receptor tyrosine kinase (RTK)-mediated signal transduction is fundamental to cell function and drives important cellular outcomes which, when dysregulated, can lead to malignant tumour growth and metastasis. The initiation of signals from plasma membrane-bound RTKs is subjected to multiple regulatory mechanisms that control downstream effector protein recruitment and function. The high propensity of RTKs to condense via liquid-liquid phase separation (LLPS) into membraneless organelles with downstream effector proteins provides a further fundamental mechanism for signal regulation. Herein we highlight how this phenomenon contributes to cancer signalling and consider the potential impact of LLPS on outcomes for cancer patients.

Keywords: cancer signalling; kinase signalling; liquid–liquid phase separation; protein condensate.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Phase Separation
  • Receptor Protein-Tyrosine Kinases* / metabolism
  • Signal Transduction*

Substances

  • Receptor Protein-Tyrosine Kinases