title: Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation.
abstract: Zinc, which is essential for many cellular processes, is controlled by zinc transporters and through buffering by metallothioneins and glutathione. Although zinc is increasingly implicated in disease states, little is known about how zinc regulates cellular biochemical pathways. Recent seminal articles have revealed discrete zinc-trafficking pathways that are linked to signalling cascades, particularly those involving protein phosphatase inhibition and downstream activation of mitogen-activated protein kinases and tyrosine kinases. Here, we discuss the mechanisms of cellular zinc homeostasis, and we propose an important role for the zinc transporter solute carrier family 39, member 7 (SLC39A7; commonly referred to as ZIP7). ZIP7 releases zinc from the endoplasmic reticulum and might be required for tyrosine kinase activation. These observations position ZIP7 at a critical node in zinc-mediated tyrosine kinase signalling and suggest that this protein might form a novel target for diseases such as cancer where prevention of tyrosine kinase activation would be therapeutically advantageous.
authors.affiliation: Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: C
authors.initials: C
authors.lastname: Hogstrand
authors.forename: P
authors.initials: P
authors.lastname: Kille
authors.forename: R I
authors.initials: RI
authors.lastname: Nicholson
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
mesh_terms: D027682:Cation Transport Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C102227:SLC39A7 protein, human; D011505:Protein-Tyrosine Kinases; D015032:Zinc