Cellular zinc signalling is triggered by CK2

Abstract

Zinc is an essential trace element involved in various biological processes. Too much or too little cellular free zinc can cause detrimental effects and cell death. The intracellular level of zinc is controlled by three groups of proteins: ZnT transporters (SLC30A, zinc exporters), ZIP channels (SLC39A, zinc importers) and zinc-binding proteins such as metallothioneins. Zinc channel, ZIP7, a hub of zinc release from the stores, has long been associated with aggressiveness and development of anti-endocrine resistance in breast cancer. However, little is known about its regulatory mechanism. Recently, we have demonstrated that this ZIP channel is post-translationally triggered by CK2 phosphorylation on two cytoplasmic residues resulting in zinc release from the stores and activation of downstream effectors which lead to cancer growth. This CK2-triggered zinc release acts to inhibit multiple protein tyrosine phosphatases, resulting in direct stimulation of normal growth, migration and, in increased amounts, also cancer growth. Interestingly, another ZIP channel, ZIP6, with a known role in EMT and cancer metastasis is also predicted to be phosphorylated by CK2. ZIP channels are therefore new substrates of CK2 that may help explain CK2-related cancer phenotypes, including cell proliferation, cell migration and metastasis.