The CD44s splice isoform is a central mediator for invadopodia activity

Pu Zhao, Yilin Xu, Yong Wei, Qiong Qiu, Teng Leong Chew, Yibin Kang, Chonghui Cheng

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1355-1365
Number of pages11
JournalJournal of cell science
Issue number7
StatePublished - Apr 1 2016

All Science Journal Classification (ASJC) codes

  • Cell Biology


  • Breast cancer
  • CD44s
  • Invadopodia
  • Metastasis
  • Splice isoform


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