Hyaluronan-CD44 Interactions Decrease the Metastatic Potential of Breast Cancer Cells.

摘要

The adhesion receptor CD44 is known to decrease the metastatic potential of breast cancer cells in vivo. This study focuses on understanding the mechanisms by which CD44 inhibits breast cancer cell invasion. We have found that the differential interaction between CD44 and soluble or embedded Hyaluronan leads to differential phosphorylation of ERK and Pak. These differentially activated signaling pathways molecularly govern a phenotypic switch between invasiveness or proliferation. Additionally, this interactions also leads to decreased transcription of the metalloprotease MMP9 when on collagen IV gels but not collagen I gels. Together, these mechanisms provide significant insight into how CD44 inhibits the movement of breast cancer cells away from their primary site.