Src SUMOylation Inhibits Tumor Growth Via Decreasing FAK Y925 Phosphorylation

Jing Wang1, Rong Deng1, Nan Cui1

  • 1Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.

Neoplasia (New York, N.Y.)
|October 26, 2017
PubMed

Insights

Src SUMOylation at lysine 318 negatively regulates its oncogenic function. This modification decreases Src-FAK complex activity, inhibiting tumor growth and cell migration.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Src is a non-receptor tyrosine kinase crucial for cell proliferation and tumorigenesis.
  • SUMOylation, a post-translational modification, significantly impacts tumor progression.

Purpose of the Study:

  • To investigate the SUMOylation of Src protein at lysine 318.
  • To elucidate the functional consequences of Src SUMOylation in cancer progression.

Main Methods:

  • In vitro and in vivo SUMOylation assays.
  • Analysis of Src phosphorylation (Y419) and focal adhesion kinase (FAK) phosphorylation (Y925).
  • Cell migration assays, soft agar assays, and tumor xenograft experiments.

Main Results:

  • Src protein undergoes SUMOylation at lysine 318.
  • Hypoxia decreases Src SUMOylation and increases Y419 phosphorylation, while hydrogen peroxide enhances SUMOylation.
  • SUMO-defective Src (K318R) expression promotes tumor growth and migration, correlating with decreased FAK Y925 phosphorylation.

Conclusions:

  • Src SUMOylation at lysine 318 negatively modulates its oncogenic function.
  • This regulation occurs, at least partially, by inhibiting Src-FAK complex activity, impacting cell migration and tumor growth.

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