A complex containing LPP and α-actinin mediates TGFβ-induced migration and invasion of ErbB2-expressing breast cancer cells

J Cell Sci. 2013 May 1;126(Pt 9):1981-91. doi: 10.1242/jcs.118315. Epub 2013 Feb 27.

Abstract

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.

Keywords: Breast cancer; EMT; ErbB2; Invasion; LPP; Migration; TGFβ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / genetics
  • Actinin / metabolism*
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Transgenic
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Neoplasm Invasiveness
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • LPP protein, human
  • Lpp protein, mouse
  • Multiprotein Complexes
  • Transforming Growth Factor beta
  • Actinin
  • ERBB2 protein, human
  • Erbb2 protein, mouse
  • Receptor, ErbB-2