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

Menachem Katz, Ido Amit, Ami Citri, Tal Shay, Silvia Carvalho, Sara Lavi, Fernanda Milanezi, Ljuba Lyass, Ninette Amariglio, Jasmine Jacob-Hirsch, Nir Ben-Chetrit, Gabi Tarcic, Moshit Lindzen, Roi Avraham, Yi Chun Liao, Patricia Trusk, Asya Lyass, Gideon Rechavi, Neil L. Spector, Su Hao LoFernando Schmitt, Sarah S. Bacus, Yosef Yarden

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

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 β1, 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.

Original languageEnglish (US)
Pages (from-to)961-969
Number of pages9
JournalNature Cell Biology
Volume9
Issue number8
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Cell Biology

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    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, N. L., ... Yarden, Y. (2007). A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. Nature Cell Biology, 9(8), 961-969. https://doi.org/10.1038/ncb1622