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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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The emerging role of receptor tyrosine kinase phase separation in cancer

Chi-Chuan Lin1, Kin Man Suen1, Jessica Lidster1

  • 1School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.

Trends in Cell Biology
|September 30, 2023
PubMed

Insights

Receptor tyrosine kinases (RTKs) regulate cell signals through liquid-liquid phase separation (LLPS). Dysregulated RTK signaling and LLPS contribute to cancer progression and metastasis, impacting patient outcomes.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Biophysics

Background:

  • Receptor tyrosine kinases (RTKs) are crucial for cell signaling, controlling cell growth and differentiation.
  • Dysregulation of RTK signaling pathways is a hallmark of many cancers, driving tumor growth and metastasis.
  • RTKs are known to undergo liquid-liquid phase separation (LLPS), forming membraneless organelles.

Purpose of the Study:

  • To elucidate the role of liquid-liquid phase separation (LLPS) in receptor tyrosine kinase (RTK) signal transduction.
  • To investigate the contribution of RTK-mediated LLPS to cancer signaling pathways.
  • To assess the potential impact of LLPS on clinical outcomes in cancer patients.

Main Methods:

  • Review of existing literature on RTK signaling and LLPS.
  • Analysis of molecular mechanisms governing RTK condensation and effector recruitment.
  • Exploration of the link between LLPS-driven signaling hubs and cancer development.

Main Results:

  • RTKs exhibit a propensity to form phase-separated condensates with downstream effectors.
  • LLPS provides a regulatory mechanism for RTK signal initiation and propagation.
  • Aberrant LLPS of RTKs can contribute to oncogenic signaling and cancer progression.

Conclusions:

  • Liquid-liquid phase separation is a fundamental mechanism regulating receptor tyrosine kinase signaling.
  • The role of LLPS in RTK function has significant implications for understanding cancer biology.
  • Targeting RTK-mediated LLPS may offer novel therapeutic strategies for cancer treatment.
Keywords:
cancer signallingkinase signallingliquid–liquid phase separationprotein condensate

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