Open AccessEzrin regulates focal adhesion and invadopodia dynamics by altering calpain activity to promote breast cancer cell invasion
Author(s) -
Victoria Hoskin,
Alvin Szeto,
Abdi Ghaffari,
Peter A. Greer,
Graham P. Côté,
Bruce E. Elliott
Publication year - 2015
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e14-12-1584
Subject(s) - ezrin , invadopodia , focal adhesion , calpain , biology , microbiology and biotechnology , cortactin , cell adhesion , cytoskeleton , cell migration , cancer research , cancer cell , paxillin , signal transduction , cancer , cell , biochemistry , genetics , enzyme
Up-regulation of the cytoskeleton linker protein ezrin frequently occurs in aggressive cancer types and is closely linked with metastatic progression. However, the underlying molecular mechanisms detailing how ezrin is involved in the invasive and metastatic phenotype remain unclear. Here we report a novel function of ezrin in regulating focal adhesion (FA) and invadopodia dynamics, two key processes required for efficient invasion to occur. We show that depletion of ezrin expression in invasive breast cancer cells impairs both FA and invadopodia turnover. We also demonstrate that ezrin-depleted cells display reduced calpain-mediated cleavage of the FA and invadopodia-associated proteins talin, focal adhesion kinase (FAK), and cortactin and reduced calpain-1–specific membrane localization, suggesting a requirement for ezrin in maintaining proper localization and activity of calpain-1. Furthermore, we show that ezrin is required for cell directionality, early lung seeding, and distant organ colonization but not primary tumor growth. Collectively our results unveil a novel mechanism by which ezrin regulates breast cancer cell invasion and metastasis.