Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion

Christa L. Cortesio, Keefe T. Chan, Benjamin J. Perrin, Nicholas O. Burton, Sheng Zhang, Zhong-Yin Zhang, Anna Huttenlocher

Research output: Contribution to journalArticle

124 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)957-971
Number of pages15
JournalJournal of Cell Biology
Volume180
Issue number5
DOIs
StatePublished - Mar 10 2008

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Calpain
Breast Neoplasms
Talin
Podosomes
2-tyrosine
Adhesives
Peptide Hydrolases
Calcium

ASJC Scopus subject areas

  • Cell Biology

Cite this

Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion. / Cortesio, Christa L.; Chan, Keefe T.; Perrin, Benjamin J.; Burton, Nicholas O.; Zhang, Sheng; Zhang, Zhong-Yin; Huttenlocher, Anna.

In: Journal of Cell Biology, Vol. 180, No. 5, 10.03.2008, p. 957-971.

Research output: Contribution to journalArticle

Cortesio, Christa L. ; Chan, Keefe T. ; Perrin, Benjamin J. ; Burton, Nicholas O. ; Zhang, Sheng ; Zhang, Zhong-Yin ; Huttenlocher, Anna. / Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion. In: Journal of Cell Biology. 2008 ; Vol. 180, No. 5. pp. 957-971.
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