Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration.
There is growing evidence that zinc and its transporters are involved in cell migration during development and in cancer. In the present study, we show that zinc transporter ZIP10 (SLC39A10) stimulates cell motility and proliferation, both in mammalian cells and in the zebrafish embryo. This is associated with inactivation of GSK (glycogen synthase kinase)-3α and -3β and down-regulation of E-cadherin (CDH1). Morpholino-mediated knockdown of zip10 causes delayed epiboly and deformities of the head, eye, heart and tail. Furthermore, zip10 deficiency results in overexpression of cdh1, zip6 and stat3, the latter gene product driving transcription of both zip6 and zip10 The non-redundant requirement of Zip6 and Zip10 for epithelial to mesenchymal transition (EMT) is consistent with our finding that they exist as a heteromer. We postulate that a subset of ZIPs carrying prion protein (PrP)-like ectodomains, including ZIP6 and ZIP10, are integral to cellular pathways and plasticity programmes, such as EMT.
Breast Cancer Molecular Pharmacology Unit, School of Pharmacy and Pharmaceutical Sciences, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, U.K. TaylorKM@cardiff.ac.uk christer.hogstrand@kcl.ac.uk.
Kathryn M
KM
Taylor
King's College London, Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences, Metal Metabolism Group, 150 Stamford St., London SE1 NH9, U.K. National Veterinary Research Institute, PMB 01 Vom, Nigeria.
Issa A
IA
Muraina
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5T 3S8 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 3H2.
Dylan
D
Brethour
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada M5T 3S8 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 3H2.
Gerold
G
Schmitt-Ulms
Breast Cancer Molecular Pharmacology Unit, School of Pharmacy and Pharmaceutical Sciences, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, U.K. Department of Pathology, Phramongkutklao College of Medicine, 315 Ratchawithi Road, Thung Phayathai, Ratchathewi, Bangkok 10400, Thailand.
Thirayost
T
Nimmanon
Breast Cancer Molecular Pharmacology Unit, School of Pharmacy and Pharmaceutical Sciences, Redwood Building, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, U.K.
Silvia
S
Ziliotto
School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AT, U.K.
Peter
P
Kille
King's College London, Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences, Metal Metabolism Group, 150 Stamford St., London SE1 NH9, U.K. TaylorKM@cardiff.ac.uk christer.hogstrand@kcl.ac.uk.
Christer
C
Hogstrand
D000818:Animals; D016466:CHO Cells; D027682:Cation Transport Proteins / Q000145:classification / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D003412:Cricetulus; D047108:Embryonic Development; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D010802:Phylogeny; D015027:Zebrafish / Q000196:embryology; D015032:Zinc / Q000378:metabolism*
D027682:Cation Transport Proteins; D015032:Zinc
SLC39A10; SLC39A6; cancer; human; mouse; zebrafish