title: A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration.
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 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.
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Katz
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.forename: Ami
authors.initials: A
authors.lastname: Citri
authors.forename: Tal
authors.initials: T
authors.lastname: Shay
authors.forename: Silvia
authors.initials: S
authors.lastname: Carvalho
authors.forename: Sara
authors.initials: S
authors.lastname: Lavi
authors.forename: Fernanda
authors.initials: F
authors.lastname: Milanezi
authors.forename: Ljuba
authors.initials: L
authors.lastname: Lyass
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Chetrit
authors.forename: Gabi
authors.initials: G
authors.lastname: Tarcic
authors.forename: Moshit
authors.initials: M
authors.lastname: Lindzen
authors.forename: Roi
authors.initials: R
authors.lastname: Avraham
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Liao
authors.forename: Patricia
authors.initials: P
authors.lastname: Trusk
authors.forename: Asya
authors.initials: A
authors.lastname: Lyass
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Neil L
authors.initials: NL
authors.lastname: Spector
authors.forename: Su Hao
authors.initials: SH
authors.lastname: Lo
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Bacus
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000070876:Tensins
chemical_list: D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D000070876:Tensins; C000603370:TNS3 protein, human; C000603371:TNS4 protein, human