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Targeting Lyn regulates Snail family shuttling and inhibits metastasis

D Thaper1,2, S Vahid1,2, K M Nip1,2

  • 1Department of Urology, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.

Oncogene
|March 14, 2017
PubMed

Insights

This study reveals Lyn kinase controls epithelial-mesenchymal transition (EMT) by regulating SNAI proteins. Targeting Lyn kinase reduces cancer metastasis and E-cadherin loss, offering a new therapeutic strategy for various cancers.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for cancer metastasis.
  • EMT involves loss of cell adhesion and polarity, often mediated by SNAI transcription factors.
  • Understanding regulators of SNAI proteins is key to inhibiting metastasis.

Purpose of the Study:

  • To identify novel regulators of SNAI protein function in EMT.
  • To investigate the role of Lyn kinase in controlling SNAI protein localization and stability.
  • To evaluate Lyn kinase as a potential therapeutic target for reducing cancer metastasis.

Main Methods:

  • Investigated Lyn kinase's role in modulating SNAI protein localization and stability.
  • Utilized the Vav-Rac1-PAK1 pathway as a mechanistic link.
  • Assessed the effect of targeting Lyn kinase on EMT in vitro and metastasis in vivo.
  • Analyzed patient cancer samples to correlate Lyn expression with E-cadherin and metastatic status.

Main Results:

  • Lyn kinase was identified as a key modulator of SNAI family protein localization and stability.
  • Targeting Lyn kinase reduced EMT in vitro and primary tumor metastasis in vivo.
  • A negative correlation between Lyn and E-cadherin was observed across multiple cancer types.
  • High Lyn expression correlated with metastatic and metastasis-prone tumors.

Conclusions:

  • Lyn kinase plays a critical role in a novel, pancancer mechanism controlling EMT.
  • Lyn kinase regulates EMT via the Vav-Rac1-PAK1 pathway, impacting SNAI protein function.
  • Targeting Lyn kinase represents a promising strategy to inhibit cancer progression and metastasis.

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