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08:02
Analysis of Cell Migration within a Three-dimensional Collagen Matrix
Published on: October 5, 2014
HER2 carboxyl-terminal fragments regulate cell migration and cortactin phosphorylation
Jesús García-Castillo1, Kim Pedersen, Pier-Davide Angelini
1Medical Oncology Research Program, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
The Journal of Biological Chemistry
|July 11, 2009
Summary
A hyperactive HER2 fragment (611-CTF) increases breast cancer cell migration. This effect is mediated by cortactin, a protein crucial for cell movement, suggesting cortactin as a therapeutic target for metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Certain breast cancer patients exhibit increased metastasis risk due to carboxyl-terminal fragments (CTFs) of the HER2 tyrosine kinase receptor.
- The 611-CTF fragment of HER2 is a hyperactive form that promotes tumor progression and metastasis by forming constitutive homodimers.
Purpose of the Study:
- To investigate the role of 611-CTF in regulating cell motility.
- To identify phosphoproteins mediating the effects of 611-CTF on cell migration.
- To explore the potential of cortactin as a therapeutic target in HER2-CTF-expressing breast tumors.
Main Methods:
- Utilized proteomic approaches, including stable isotope labeling with amino acids in cell culture (SILAC) and difference gel electrophoresis (DIGE).
- Employed DIGE to identify changes in multiphosphorylated proteins, specifically screening for mediators of 611-CTF's effect on cell motility.
- Validated findings through characterization of cortactin in cells expressing 611-CTF and cortactin knockdown experiments.
Main Results:
- Expression of 611-CTF significantly increased cell motility across various assays.
- Proteomic screening identified cortactin, a cytoskeleton-binding protein, as a likely downstream target regulated by 611-CTF phosphorylation.
- Knockdown of cortactin effectively inhibited 611-CTF-induced cell migration.
Conclusions:
- Cortactin is identified as a key mediator of 611-CTF-induced cell migration in breast cancer.
- The 611-CTF/cortactin pathway plays a significant role in the metastatic behavior of breast tumors.
- Targeting cortactin may represent a novel therapeutic strategy for managing metastasis in specific breast cancer subtypes.
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