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Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification (BiCAP)
Published on: June 15, 2018
c-Src modulates ErbB2 and ErbB3 heterocomplex formation and function
R C Ishizawar1, T Miyake, S J Parsons
1Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
Oncogene
|December 19, 2006
Summary
The study reveals that c-Src kinase enhances the interaction between ErbB2 and ErbB3 receptors, boosting breast cancer cell growth and motility. Inhibiting c-Src disrupts this oncogenic signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Overexpression of c-Src and epidermal growth factor receptor (EGFR/ErbB) family members is linked to breast cancer development.
- EGFR/ErbB family members form heterocomplexes, and c-Src physically interacts with them in breast cancer.
- The ErbB2/ErbB3 heterocomplex exhibits significant oncogenic potential.
Purpose of the Study:
- To investigate the role of c-Src in modulating the physical and functional interaction between ErbB2 and ErbB3.
- To determine if c-Src acts upstream or downstream of ErbB2/ErbB3 signaling.
- To elucidate the impact of c-Src on the oncogenic functions mediated by the ErbB2/ErbB3 heterocomplex.
Main Methods:
- Overexpression of wild-type and kinase-inactive c-Src (K(-) c-Src) in breast cancer cells.
- Pharmacological inhibition of c-Src using PP2.
- Assessment of ErbB2/ErbB3 heterocomplex formation and receptor activation.
- Evaluation of downstream signaling pathways and cellular functions like motility and anchorage-independent growth.
Main Results:
- Overexpressed wild-type c-Src enhances ErbB2/ErbB3 heterocomplex formation.
- This enhancement leads to increased basal and heregulin-induced activation of ErbB2/ErbB3 and downstream effectors.
- Inhibition or inactivation of c-Src abrogates ErbB2/ErbB3-mediated cellular motility and anchorage-independent growth.
- c-Src positively modulates ErbB2/ErbB3 association, suggesting an upstream role.
Conclusions:
- c-Src plays a critical upstream role in enhancing ErbB2/ErbB3 signaling and oncogenic functions in breast cancer.
- Modulation of ErbB2/ErbB3 association by c-Src is a key mechanism driving tumor progression.
- Targeting c-Src may represent a therapeutic strategy for breast cancers driven by ErbB2/ErbB3 signaling.
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