Talin regulates moesin-NHE-1 recruitment to invadopodia and promotes mammary tumor metastasis

Brian T. Beaty, Yarong Wang, Jose Javier Bravo-Cordero, Ved P. Sharma, Veronika Miskolci, Louis Hodgson, John S. Condeelis

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Invadopodia are actin-rich protrusions that degrade the extracellular matrix and are required for stromal invasion, intravasation, and metastasis. The role of the focal adhesion protein talin in regulating these structures is not known. Here, we demonstrate that talin is required for invadopodial matrix degradation and three-dimensional extracellular matrix invasion in metastatic breast cancer cells. The sodium/hydrogen exchanger 1 (NHE-1) is linked to the cytoskeleton by ezrin/radixin/moesin family proteins and is known to regulate invadopodium-mediated matrix degradation. We show that the talin C terminus binds directly to the moesin band 4.1 ERM (FERM) domain to recruit a moesin-NHE-1 complex to invadopodia. Silencing talin resulted in a decrease in cytosolic pH at invadopodia and blocked cofilin-dependent actin polymerization, leading to impaired invadopodium stability and matrix degradation. Furthermore, talin is required for mammary tumor cell motility, intravasation, and spontaneous lung metastasis in vivo. Thus, our findings provide a novel understanding of how intracellular pH is regulated and a molecular mechanism by which talin enhances tumor cell invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)737-751
Number of pages15
JournalJournal of Cell Biology
Volume205
Issue number5
DOIs
StatePublished - 2014

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Talin
Breast Neoplasms
Neoplasm Metastasis
Extracellular Matrix
Actins
Actin Depolymerizing Factors
Sodium-Hydrogen Antiporter
Focal Adhesions
Cytoskeleton
Polymerization
Cell Movement
moesin
Podosomes
Proteins
Lung

ASJC Scopus subject areas

  • Cell Biology

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Talin regulates moesin-NHE-1 recruitment to invadopodia and promotes mammary tumor metastasis. / Beaty, Brian T.; Wang, Yarong; Bravo-Cordero, Jose Javier; Sharma, Ved P.; Miskolci, Veronika; Hodgson, Louis; Condeelis, John S.

In: Journal of Cell Biology, Vol. 205, No. 5, 2014, p. 737-751.

Research output: Contribution to journalArticle

Beaty, Brian T. ; Wang, Yarong ; Bravo-Cordero, Jose Javier ; Sharma, Ved P. ; Miskolci, Veronika ; Hodgson, Louis ; Condeelis, John S. / Talin regulates moesin-NHE-1 recruitment to invadopodia and promotes mammary tumor metastasis. In: Journal of Cell Biology. 2014 ; Vol. 205, No. 5. pp. 737-751.
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