Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada.
J Cell Sci. 2013 May 1;126(Pt 9):1981-91. doi: 10.1242/jcs.118315. Epub 2013 Feb 27.
Transforming growth factor β (TGFβ) is a potent modifier of the malignant phenotype in ErbB2-expressing breast cancers. We demonstrate that epithelial-derived breast cancer cells, which undergo a TGFβ-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 TGFβ-induced migration and invasion of ErbB2-expressing breast cancer cells. We show that LPP re-localizes to focal adhesion complexes upon TGFβ stimulation and is a critical determinant in TGFβ-mediated focal adhesion turnover. Finally, we have determined that the interaction between LPP and α-actinin, an actin cross-linking protein, is necessary for TGFβ-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.
转化生长因子 β（TGFβ）是 ErbB2 表达的乳腺癌中恶性表型的有效调节剂。我们证明，上皮来源的乳腺癌细胞经历 TGFβ 诱导的上皮-间充质转化（EMT），会利用通常促进间质细胞迁移和侵袭的信号分子。我们确定脂肪细胞优先伙伴（LPP）是 TGFβ 诱导 ErbB2 表达的乳腺癌细胞迁移和侵袭所必需的调节剂。我们表明，LPP 在 TGFβ 刺激下重新定位于粘着斑复合物，并且是 TGFβ 介导的粘着斑周转中的关键决定因素。最后，我们已经确定 LPP 与肌动蛋白交联蛋白α-辅肌动蛋白之间的相互作用对于 TGFβ 诱导的 ErbB2 表达的乳腺癌细胞的迁移和侵袭是必需的。因此，我们的数据表明，正常在上皮细胞中起作用的 LPP，在 EMT 期间可以被乳腺癌细胞“借用”来促进其迁移和侵袭。
