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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell
Christa L Cortesio1, Keefe T Chan, Benjamin J Perrin
1Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA.
Abstract:
Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel function for calpain 2 in the formation of invadopodia and in the invasive abilities of breast cancer cells through the modulation of endogenous c-Src activity. Calpain-deficient breast cancer cells show impaired invadopodia formation that is rescued by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B) corresponding to the calpain proteolytic fragment, which indicates that calpain modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for efficient invadopodia formation and breast cancer invasion, which suggests that PTP1B may modulate breast cancer progression through its effects on invadopodia. Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion.
Insights
Calpain 2 and protein tyrosine phosphatase 1B (PTP1B) are crucial for invadopodia formation and breast cancer cell invasion. This study reveals a novel signaling pathway regulating these processes.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Invadopodia are critical structures for cancer cell invasion and matrix degradation.
- Calpain 2, a calcium-dependent protease, regulates cell adhesion dynamics.
- The role of calpain 2 in invadopodia formation and breast cancer invasion was previously unclear.
Purpose of the Study:
- To investigate the novel function of calpain 2 in invadopodia formation and breast cancer cell invasion.
- To elucidate the signaling pathway involving calpain 2, PTP1B, and c-Src in regulating these processes.
Main Methods:
- Utilized calpain-deficient breast cancer cells.
- Assessed invadopodia formation and invasive abilities.
- Investigated the role of protein tyrosine phosphatase 1B (PTP1B) and c-Src activity.
Main Results:
- Calpain-deficient cells exhibited impaired invadopodia formation.
- Expression of a PTP1B fragment rescued invadopodia formation in calpain-deficient cells.
- PTP1B activity was essential for efficient invadopodia formation and breast cancer invasion.
Conclusions:
- Calpain 2 regulates invadopodia formation and breast cancer invasion through PTP1B and c-Src.
- PTP1B plays a significant role in breast cancer progression via invadopodia modulation.
- A novel signaling pathway involving calpain 2, PTP1B, and Src is implicated in breast cancer invasion.
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