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

• Type: Article in International Scientific Journal
• Date: 2007

Authors

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

Journal

Title: Nature Cell Biology

Vol. 9

Pages: 961-U124

ISSN: 1465-7392

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 157 Citations

Scopus - 161 Citations

Other information

Authenticus ID: P-004-8KQ

DOI: 10.1038/ncb1622

Abstract (EN): Cell migration driven by the epidermal growth factor receptor ( EGFR) propels morphogenesis(1) and involves reorganization of the actin cytoskeleton(2). Although de novo transcription precedes migration(3,4), transcript identity remains largely unknown. Through their actin-binding domains, tensins link the cytoskeleton to integrin-based adhesion sites(5). Here we report that EGF downregulates tensin-3 expression, and concomitantly upregulates cten, a tensin family member that lacks the actin-binding domain(6). Knockdown of cten or tensin-3, respectively, impairs or enhances mammary cell migration. Furthermore, cten displaces tensin-3 from the cytoplasmic tail of integrin beta(1), 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14