Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

A mechanism for epithelial–mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3)

Hogstrand, Christer, Kille, Peter, Ackland, Margaret Leigh, Hiscox, Stephen Edward and Taylor, Kathryn Mary 2013. A mechanism for epithelial–mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3). Biochemical Journal 455 (2) , pp. 229-237. 10.1042/BJ20130483

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Genes involved in normal developmental processes attract attention as mediators of tumour progression as they facilitate migration of tumour cells. Epithelial-mesenchymal transition (EMT), an essential part of embryonic development, tissue remodelling and wound repair, is crucial for tumour metastasis. Previously zinc transporter ZIP6 (SLC39A6, LIV-1) was linked to EMT in zebrafish gastrulation through a STAT3 mechanism resulting in nuclear localisation of transcription factor Snail. Here we show that zinc transporter ZIP6 is transcriptionally induced by STAT3 and unprecedented among zinc transporters is activated by N-terminal cleavage which triggers ZIP6 plasma membrane location and zinc influx. This zinc influx inactivates GSK-3β, either indirectly or directly via AKT or GSK-3β, respectively, resulting in activation of Snail, which remains in the nucleus and acts as a transcriptional repressor of E-cadherin, CDH1, causing cell rounding and detachment. This was mirrored by ZIP6-transfected cells which underwent EMT, detached from monolayers and exhibited resistance to anoikis by their ability to continue proliferating even after detachment. Our results indicate a causative role for ZIP6 in cell motility and migration, providing ZIP6 as a new target for prediction of clinical cancer spread and also suggesting a ZIP6-dependant mechanism of tumour metastasis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Pharmacy
Subjects: Q Science > Q Science (General)
Q Science > QP Physiology
Uncontrolled Keywords: breast cancer; cell detachment; epithelial–mesenchymal transition (EMT); LIV-1; signal transducer and activator of transcription 3 (STAT3); solute carrier family 39; member 6 (SLC39A6); ZIP6
Publisher: Portland Press
ISSN: 0264-6021
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Last Modified: 15 Nov 2017 22:42
URI: http://orca-mwe.cf.ac.uk/id/eprint/50347

Citation Data

Cited 54 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics