A complex containing LPP and &agr;-actinin mediates TGF&bgr;-induced migration and invasion of ErbB2-expressing breast cancer cells

Summary Transforming growth factor &bgr; (TGF&bgr;) is a potent modifier of the malignant phenotype in ErbB2-expressing breast cancers. We demonstrate that epithelial-derived breast cancer cells, which undergo a TGF&bgr;-induced epithelial-to-mesenchymal transition (EMT), engage signaling molecules that normally facilitate cellular migration and invasion of mesenchymal cells. We identify lipoma preferred partner (LPP) as an indispensable regulator of TGF&bgr;-induced migration and invasion of ErbB2-expressing breast cancer cells. We show that LPP re-localizes to focal adhesion complexes upon TGF&bgr; stimulation and is a critical determinant in TGF&bgr;-mediated focal adhesion turnover. Finally, we have determined that the interaction between LPP and &agr;-actinin, an actin cross-linking protein, is necessary for TGF&bgr;-induced migration and invasion of ErbB2-expressing breast cancer cells. Thus, our data reveal that LPP, which is normally operative in cells of mesenchymal origin, can be co-opted by breast cancer cells during an EMT to promote their migration and invasion.

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