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
Date Published2016 Apr 01
KeywordsAnimals, Breast Neoplasms, Cell Line, Tumor, Cortactin, Female, Humans, Hyaluronan Receptors, Lung Neoplasms, Matrix Metalloproteinase 14, MCF-7 Cells, Mice, Mice, Nude, Neoplasm Invasiveness, Neoplasm Transplantation, NIH 3T3 Cells, Phosphorylation, Podosomes, Protein Isoforms, RNA Interference, RNA, Small Interfering, Transplantation, Heterologous

<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>

Alternate JournalJ Cell Sci
PubMed ID26869223
PubMed Central IDPMC6518308
Grant ListP30 CA060553 / CA / NCI NIH HHS / United States
R01 CA141062 / CA / NCI NIH HHS / United States
R01CA182467 / CA / NCI NIH HHS / United States
R01 CA182467 / CA / NCI NIH HHS / United States
R01CA141062 / CA / NCI NIH HHS / United States