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Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation

Xiuquan Ma1,2, Luxi Zhang1,2, Jiangning Song2,3,4

  • 1Cancer Program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia.

Nature Communications
|January 19, 2019
PubMed

Insights

This study reveals how oncogenes like Src drive cell transformation by altering protein kinases. Targeting both Src and SGK1 kinase shows promise for improved breast cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • Understanding oncogene-induced cell transformation is crucial for cancer therapy.
  • The complexity of downstream signaling pathways remains incompletely understood.

Purpose of the Study:

  • To globally characterize the impact of oncogenes on the kinome using chemical proteomics.
  • To identify essential kinases for oncogenic transformation and therapeutic targets.

Main Methods:

  • Mass spectrometry-based chemical proteomics to analyze the kinome.
  • Functional annotation of regulated kinases.
  • siRNA screening to identify essential kinases for transformation.

Main Results:

  • Identified 63 protein kinases with altered expression or phosphorylation in Src-transformed cells.
  • Discovered nine essential kinases, including SGK1, for Src-induced transformation.
  • Demonstrated that Src positively regulates SGK1 in triple-negative breast cancer cells.

Conclusions:

  • The developed approach provides mechanistic insights into oncogenic transformation.
  • Combined inhibition of Src and SGK1 is more effective than single inhibition for reducing tumor growth.
  • This strategy aids in designing improved therapeutic strategies for cancers driven by oncogenes like Src.

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