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

被引:153
作者
Cortesio, Christa L. [1 ,2 ,3 ]
Chan, Keefe T. [1 ,3 ]
Perrin, Benjamin J. [1 ,3 ]
Burton, Nicholas O. [1 ,3 ]
Zhang, Sheng [4 ]
Zhang, Zhong-Yin [4 ]
Huttenlocher, Anna [1 ,3 ]
机构
[1] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Biol Chem, Madison, WI 53706 USA
[3] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA
[4] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA
关键词
D O I
10.1083/jcb.200708048
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:957 / 971
页数:15
相关论文
共 50 条
[1]   Impaired integrin-mediated adhesion and signaling in fibroblasts expressing a dominant-negative mutant PTP1B [J].
Arregui, CO ;
Balsamo, J ;
Lilien, J .
JOURNAL OF CELL BIOLOGY, 1998, 143 (03) :861-873
[2]   Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: Defining the stages of invadopodia formation and function [J].
Artym, VV ;
Zhang, Y ;
Seillier-Moiseiwitsch, FO ;
Yamada, KM ;
Mueller, SC .
CANCER RESEARCH, 2006, 66 (06) :3034-3043
[3]   Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer [J].
Bentires-Alj, Mohamed ;
Neel, Benjamin G. .
CANCER RESEARCH, 2007, 67 (06) :2420-2424
[4]  
Bhatt AK, 2003, METHOD ENZYMOL, V361, P337
[5]   Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines [J].
Bjorge, JD ;
Pang, A ;
Fujita, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (52) :41439-41446
[6]   Foot and mouth: Podosomes, invadopodia and circular dorsal ruffles [J].
Buccione, R ;
Orth, JD ;
McNiven, MA .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (08) :647-657
[7]   Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells [J].
Calle, Y ;
Chou, HC ;
Thrasher, AJ ;
Jones, GE .
JOURNAL OF PATHOLOGY, 2004, 204 (04) :460-469
[8]   Inhibition of calpain stabilises podosomes and impairs dendritic cell motility [J].
Calle, Yolanda ;
Carragher, Neil O. ;
Thrasher, Adrian J. ;
Jones, Gareth E. .
JOURNAL OF CELL SCIENCE, 2006, 119 (11) :2375-2385
[9]   Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function [J].
Carragher, N. O. ;
Walker, S. M. ;
Carragher, L. A. Scott ;
Harris, F. ;
Sawyer, T. K. ;
Brunton, V. G. ;
Ozanne, B. W. ;
Frame, M. C. .
ONCOGENE, 2006, 25 (42) :5726-5740
[10]   Calpain activity is generally elevated during transformation but has oncogene-specific biological functions [J].
Carragher, NO ;
Fonseca, BD ;
Frame, MC .
NEOPLASIA, 2004, 6 (01) :53-73