The CD44s splice isoform is a central mediator for invadopodia activity.

TitleThe CD44s splice isoform is a central mediator for invadopodia activity.
Publication TypeJournal Article
Year of Publication2016
AuthorsZhao, P, Xu, Y, Wei, Y, Qiu, Q, Chew, T-L, Kang, Y, Cheng, C
JournalJ Cell Sci
Volume129
Issue7
Pagination1355-65
Date Published2016 Apr 1
ISSN1477-9137
Abstract

<p>The ability for tumor cells to spread and metastasize to distant organs requires proteolytic degradation of extracellular matrix (ECM). This activity is mediated by invadopodia, actin-rich membrane protrusions that are enriched for proteases. However, the mechanisms underlying invadopodia activity are not fully understood. Here, we report that a specific CD44 splice isoform, CD44s, is an integral component in invadopodia. We show that CD44s, but not another splice isoform CD44v, is localized in invadopodia. Small hairpin (sh)RNA-mediated depletion of CD44s abolishes invadopodia activity, prevents matrix degradation and decreases tumor cell invasiveness. Our results suggest that CD44s promotes cortactin phosphorylation and recruits MT1-MMP (also known as MMP14) to sites of matrix degradation, which are important activities for invadopodia function. Importantly, we show that depletion of CD44s inhibits breast cancer cell metastasis to the lung in animals. These findings suggest a crucial mechanism underlying the role of the CD44s splice isoform in breast cancer metastasis.</p>

DOI10.1242/jcs.171959
Alternate JournalJ. Cell. Sci.
PubMed ID26869223
Grant ListP30 CA060553 / CA / NCI NIH HHS / United States
R01CA141062 / CA / NCI NIH HHS / United States
R01CA182467 / CA / NCI NIH HHS / United States