A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration.


Journal Article

Cell migration driven by the epidermal growth factor receptor (EGFR) propels morphogenesis and involves reorganization of the actin cytoskeleton. Although de novo transcription precedes migration, transcript identity remains largely unknown. Through their actin-binding domains, tensins link the cytoskeleton to integrin-based adhesion sites. Here we report that EGF downregulates tensin-3 expression, and concomitantly upregulates cten, a tensin family member that lacks the actin-binding domain. Knockdown of cten or tensin-3, respectively, impairs or enhances mammary cell migration. Furthermore, cten displaces tensin-3 from the cytoplasmic tail of integrin beta1, thereby instigating actin fibre disassembly. In invasive breast cancer, cten expression correlates not only with high EGFR and HER2, but also with metastasis to lymph nodes. Moreover, treatment of inflammatory breast cancer patients with an EGFR/HER2 dual-specificity kinase inhibitor significantly downregulated cten expression. In conclusion, a transcriptional tensin-3-cten switch may contribute to the metastasis of mammary cancer.

Full Text

Duke Authors

Cited Authors

  • Katz, M; Amit, I; Citri, A; Shay, T; Carvalho, S; Lavi, S; Milanezi, F; Lyass, L; Amariglio, N; Jacob-Hirsch, J; Ben-Chetrit, N; Tarcic, G; Lindzen, M; Avraham, R; Liao, Y-C; Trusk, P; Lyass, A; Rechavi, G; Spector, NL; Lo, SH; Schmitt, F; Bacus, SS; Yarden, Y

Published Date

  • August 2007

Published In

Volume / Issue

  • 9 / 8

Start / End Page

  • 961 - 969

PubMed ID

  • 17643115

Pubmed Central ID

  • 17643115

International Standard Serial Number (ISSN)

  • 1465-7392

Digital Object Identifier (DOI)

  • 10.1038/ncb1622


  • eng

Conference Location

  • England