MenaINV dysregulates cortactin phosphorylation to promote invadopodium maturation
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Mena(INV).pdf
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Author(s)
Weidmann, Maxwell D.
Surve, Chinmay R.
Eddy, Robert J.
Chen, Xiaoming
Sharma, Ved P.
Condeelis, John S.
Gertler, Frank
Date Issued
November 2016
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Weidmann, Maxwell D.; Surve, Chinmay R.; Eddy, Robert J.; Chen, Xiaoming; Gertler, Frank B.; Sharma, Ved P. and Condeelis, John S. “MenaINV Dysregulates Cortactin Phosphorylation to Promote Invadopodium Maturation.” Scientific Reports 6, no. 1 (November 8, 2016). © 2016 Macmillan Publishers Limited, part of Springer Nature
Version
Final published version
Abstract
Invadopodia, actin-based protrusions of invasive carcinoma cells that focally activate extracellular matrix-degrading proteases, are essential for the migration and intravasation of tumor cells during dissemination from the primary tumor. We have previously shown that cortactin phosphorylation at tyrosine residues, in particular tyrosine 421, promotes actin polymerization at newly-forming invadopodia, promoting their maturation to matrix-degrading structures. However, the mechanism by which cells regulate the cortactin tyrosine phosphorylation-dephosphorylation cycle at invadopodia is unknown. Mena, an actin barbed-end capping protein antagonist, is expressed as various splice-isoforms. The MenaINV isoform is upregulated in migratory and invasive sub-populations of breast carcinoma cells, and is involved in tumor cell intravasation. Here we show that forced MenaINV expression increases invadopodium maturation to a far greater extent than equivalent expression of other Mena isoforms. MenaINV is recruited to invadopodium precursors just after their initial assembly at the plasma membrane, and promotes the phosphorylation of cortactin tyrosine 421 at invadopodia. In addition, we show that cortactin phosphorylation at tyrosine 421 is suppressed by the phosphatase PTP1B, and that PTP1B localization to the invadopodium is reduced by MenaINV expression. We conclude that MenaINV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/srep36142
