Letter abstract
Nature Cell Biology 9, 961 - 969 (2007)
Published online: 22 July 2007 | doi:10.1038/ncb1622
A reciprocal tensin-3–cten switch mediates EGF-driven mammary cell migration
Menachem Katz1, Ido Amit1, Ami Citri1, Tal Shay2, Silvia Carvalho3, Sara Lavi1, Fernanda Milanezi3, Ljuba Lyass4, Ninette Amariglio5, Jasmine Jacob-Hirsch5, Nir Ben-Chetrit1, Gabi Tarcic1, Moshit Lindzen1, Roi Avraham1, Yi-Chun Liao6, Patricia Trusk4, Asya Lyass7, Gideon Rechavi5, Neil L. Spector8, Su Hao Lo6, Fernando Schmitt3,9, Sarah S. Bacus4 & Yosef Yarden1
Cell migration driven by the epidermal growth factor receptor (EGFR) propels morphogenesis1 and involves reorganization of the actin cytoskeleton2. Although de novo transcription precedes migration3, 4, transcript identity remains largely unknown. Through their actin-binding domains, tensins link the cytoskeleton to integrin-based adhesion sites5. Here we report that EGF downregulates tensin-3 expression, and concomitantly upregulates cten, a tensin family member that lacks the actin-binding domain6. Knockdown of cten or tensin-3, respectively, impairs or enhances mammary cell migration. Furthermore, cten displaces tensin-3 from the cytoplasmic tail of integrin 
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.
- Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
- Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100, Israel
- IPATIMUP – Institute of Molecular Pathology and Immunology of the University of Porto, Porto 4200-465, Portugal
- Targeted Molecular Diagnostics, Westmont, Illinois 60559, USA
- Department of Pediatric Hemato-Oncology and Functional Genomics, The Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California-Davis, Sacramento, California 95817, USA
- Boston University, Boston, Massachusetts 02215, USA
- Department of Exploratory Medical Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina 27709
- Medical Faculty of Porto University, Porto 4200-465, Portugal
Correspondence to: Yosef Yarden1 e-mail: yosef.yarden@weizmann.ac.il
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