Matriptase Activation in Breast Cancer Progression
Abstract
In the current research plan, we proposed to study the mechanism for activation of matriptase, a membrane-bound serine protease. Previously, we showed matriptase is activated via transactivation, where the interactions among latent matriptase molecules, HAI-1, and other unidentified proteins are required for the proceeding of activational cleavage. in non-transformed mammary epithelial cells, matriptase activation can be Induced by sphingosine 1-phosphate (sip), a blood-borne bioactive phospholipid. in the past one-year, we further showed that Sip induces matriptase translocation and accumulation at cell-cell contacts where activation occurs. We further showed that both matriptase translocation and activation depend on the assembly of adherens junctions and formation of subcortical actin belts in response to Sip exposure. Disruption of subcortical act in belt formation and prevention of adherens junction assembly led to prevention of accumulation and activation of the protease at cell-cell contacts. The coupling of matriptase activation to adherens junction assembly and actin cytoskeletal rearrangement may serve to ensure tight control of matriptase activity, restricted to cell-cell junctions of mammary epithelial cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427164
Entities
People
- Chen-yong Lin
Organizations
- Georgetown University