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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Yarong Sharma, Ved P. Miskolci, Veronika Hodgson, Louis Bravo-cordero, Jose Javier Condeelis, John Beaty, Brian T. |
| Description | Author Affiliation: Beaty BT ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461 brian.beaty@med.einstein.yu.edu john.condeelis@einstein.yu.edu.); Wang Y ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461.); Bravo-Cordero JJ ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, B); Sharma VP ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, B); Miskolci V ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461.); Hodgson L ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, B); Condeelis J ( Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, B) |
| 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. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 205 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2014-06-09 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cation Transport Proteins Metabolism Mammary Neoplasms, Experimental Microfilament Proteins Sodium-Hydrogen Antiporter Talin Actins Animals Binding Sites Breast Neoplasms Cell Line, Tumor Cell Movement Cytoskeletal Proteins Cytoskeleton Extracellular Matrix Gene Expression Regulation, Neoplastic Gene Silencing Hydrogen-Ion Concentration Lung Neoplasms Membrane Proteins Mice Mice, SCID Neoplasm Metastasis Protein Structure, Tertiary RNA, Small Interfering Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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