The CD44s splice isoform is a central mediator for invadopodia activity
Abstract
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 CD44v is localized in invadopodia. shRNA-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 to sites of matrix degradation, 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2016
- Source ID
- 10.1242/jcs.171959
Entities
People
- Chonghui Cheng
- Pu Zhao
- Qiong Qiu
- Teng-leong Chew
- Yibin Kang
- Yilin Xu
- Yong Wei
Organizations
- American Cancer Society
- Feinberg School of Medicine
- National Cancer Institute
- National Natural Science Foundation of China
- Northwestern University
- Princeton University
- United States Department of Defense