Abstract
The plasma membrane is a key actor of cell migration. For instance, its tension controls persistent cell migration and cell surface caveolae integrity. Then, caveolae constituents like caveolin-1 can initiate a mechano-tranduction loop that involves actin-and focal adhesions- dependent control of the mechanosensor YAP to finely tune cell migration. Tetraspanin CD82 (also named KAI-1) is an integral membrane protein and a metastasis suppressor. Its expression is lost in many cancers including breast cancer. It is a strong inhibitor of cell migration by a not well-known mechanism. We demonstrated here that CD82 controls persistent 2D migration of EGF-induced single cell, stress fibers and focal adhesion sizes and dynamics. In addition, CD82 regulates cell mechanics e.g. membrane tension, cell surface caveolae abundance and YAP nuclear translocation in a caveolin-1 dependent manner. Altogether, our data strongly suggest that CD82 controls 2D cell migration using a membrane-driven mechanical loop involving caveolin and the YAP pathway.
Highlights
Cell migration is a necessary process during embryonic development and can be subverted in pathologies such as cancer metastasis
A similar pattern in membrane projections was observed in MCF10a cells (Figure 3E, lower panels). These results clearly indicate that CD82 is expressed at the plasma membrane, where it can regulate cell migration, actin stress fiber sizes and focal adhesion dynamics
Since caveolae are membrane invaginations that behave as physiological membrane reservoirs and can buffer membrane tension induced by mechanical stress [18], we have studied the effect of CD82 expression on the density of caveolae at the cell surface of HB2, HB2CD82 and MCF10a cells
Summary
Cell migration is a necessary process during embryonic development and can be subverted in pathologies such as cancer metastasis. Major steps in carcinoma metastasis are: (1) epithelial cells are released from cell–cell contacts by epithelial-to-mesenchymal transition (EMT); (2) cell migration across the basement membrane and underlying tissues;. (3) intravasation into blood vessels and extravasation from blood vessels to the metastasis place; and (4) establishment of metastatic niches, mesenchymal to epithelial transition (MET), and dormancy or aberrant proliferation [1]. Tetraspanin CD82, named KAI1, falls into this category [3]. It is a member of the tetraspanin family (33 members) which are characterized by four transmembrane domains that separate two extracellular domains. Most tetraspanins are glycosylated on extracellular domains and palmitoylated at juxtamembrane intracellular cysteines
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