A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration.
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.
Katz
Menachem
M
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Amit
Ido
I
Citri
Ami
A
Shay
Tal
T
Carvalho
Silvia
S
Lavi
Sara
S
Milanezi
Fernanda
F
Lyass
Ljuba
L
Amariglio
Ninette
N
Jacob-Hirsch
Jasmine
J
Ben-Chetrit
Nir
N
Tarcic
Gabi
G
Lindzen
Moshit
M
Avraham
Roi
R
Liao
Yi-Chun
YC
Trusk
Patricia
P
Lyass
Asya
A
Rechavi
Gideon
G
Spector
Neil L
NL
Lo
Su Hao
SH
Schmitt
Fernando
F
Bacus
Sarah S
SS
Yarden
Yosef
Y
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
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