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Published on: November 1, 2019
Src SUMOylation Inhibits Tumor Growth Via Decreasing FAK Y925 Phosphorylation
Abstract:
Src, a non-receptor tyrosine kinase protein, plays a critical role in cell proliferation and tumorigenesis. SUMOylation, a reversible ubiquitination-like post-translational modification, is vital for tumor progression. Here, we report that the Src protein can be SUMOylated at lysine 318 both in vitro and in vivo. Hypoxia can induce a decrease of Src SUMOylation along with an increase of Y419 phosphorylation, a phosphorylation event required for Src activation. On the other hand, treatment with hydrogen peroxide can enhance Src SUMOylation. Significantly, ectopic expression of SUMO-defective mutation, Src K318R, promotes tumor growth more potently than that of wild-type Src, as determined by migration assay, soft agar assay, and tumor xenograft experiments. Consistently, Src SUMOylation leads to a decrease of Y925 phosphorylation of focal adhesion kinase (FAK), an established regulatory event of cell migration. Our results suggest that SUMOylation of Src at lysine 318 negatively modulate its oncogenic function by, at least partially, inhibiting Src-FAK complex activity.
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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