Cell movement

Tetraspanins signal invasion

Science's STKE  05 Oct 1999:
Vol. 1999, Issue 2, pp. tw3
DOI: 10.1126/stke.1999.2.tw3

The invasive behavior of tumor cells is attributed in part to their ability to break down their surrounding extracellular matrix (ECM). Integrins, the cell surface receptors for the ECM, are thought to regulate the production of ECM-degrading enzymes called matrix metalloproteinases (MMPs). Sugiura and Berdichevski have now found that cell surface proteins called tetraspanins form a complex with the α3β3 integrin in a mammary epithelial tumor cell line, and that activation of this protein complex with specific antibodies stimulated the cells to secrete MMP-2. The α3β3-tetraspanin complexes were found at the tips of cellular extensions that further penetrated into the surrounding matrix upon activation of the complex. Because an inhibitor of phosphoinositide 3-kinase (PI3K) reduced the stimulatory effects of the complex-specific antibodies, the authors propose that tumor invasion may be regulated by activation of a PI3K-dependent signaling pathway that is controlled by integrin-tetraspanin complexes.

Ugiura, T., and Berdichevski, F. (1999) Function of α3β3-tetraspanin complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2 (MMP-2). J Cell Biol. 146: 1375-1389. [Abstract] [Full Text]