Function of the integrin α6β1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor

The involvement of the α6β1 integrin, a laminin receptor, in breast carcinoma progression needs to be addressed rigorously. We report that a human breast carcinoma cell line, MDA-MB-435, known to be highly invasive and metastatic, expresses three potential integrin laminin receptors: α2β1, α3β1, and α6β1, but uses only α6β1 to mediate adhesion and migration on laminin matrices. To investigate the contribution of α6β1 to the aggressive behavior of these cells, we developed a dominant-negative strategy for knocking out α6β1 function that involved expression of a cytoplasmic domain deletion mutant of the β4 integrin subunit by cDNA transfection. Stable transfectants of MDA-MB-435 cells that expressed this mutant β4 subunit were inhibited dramatically in their ability to adhere and migrate on laminin matrices, and their capacity to invade Matrigel was reduced significantly. These findings support the hypothesis that α6β1 is important for breast cancer progression. Moreover, this approach is a powerful method that should be useful in assessing the role of α6β1 in other cells.