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Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
Integrin alpha v beta 3 controls activity and oncogenic potential of primed c-Src
Stephan Huveneers1, Iman van den Bout, Petra Sonneveld
1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Cancer Research
|March 17, 2007
Summary
Integrin alpha(v)beta(3) activates primed c-Src, a proto-oncogene crucial for cancer growth. This interaction, mediated by the beta(3) cytoplasmic tail and c-Src SH3 domain, offers a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Proto-oncogene c-Src activity and integrin alpha(v)beta(3) levels are elevated in various cancers.
- c-Src regulation involves priming and activation via phosphorylation.
- Cancer-associated factors like RTKs or SRC mutations can prime c-Src.
Purpose of the Study:
- To investigate the role of integrin alpha(v)beta(3) in promoting c-Src activation.
- To elucidate the mechanism by which alpha(v)beta(3) influences c-Src activity and downstream effects.
- To identify potential therapeutic targets within this signaling pathway.
Main Methods:
- Utilized cancer cell lines with elevated c-Src and integrin alpha(v)beta(3).
- Employed Src variants, including those with v-Src SH3 domains, and mutant beta(3) subunits.
- Assessed phosphorylation of Src substrates, cell survival, proliferation, and tumor growth.
Main Results:
- alpha(v)beta(3) promotes the activation of primed c-Src.
- This activation leads to enhanced Src substrate phosphorylation, increased cell survival, proliferation, and tumor growth.
- The beta(3) cytoplasmic tail is essential and sufficient for this stimulation, independent of beta(3) tyrosine phosphorylation.
- A functional interaction between the beta(3) cytoplasmic tail and the c-Src SH3 domain is critical.
Conclusions:
- Integrin alpha(v)beta(3) plays a key role in oncogenic signaling by activating c-Src.
- The interaction between alpha(v)beta(3) and c-Src represents a novel signaling cascade.
- Targeting the alpha(v)beta(3)-c-Src interaction may offer a new therapeutic strategy for cancers.
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