Professor Will Brackenbury 

Research

Overview

Our lab explores the role of ion channels in disease, focussing on how aberrant ion channel signalling can alter cell behaviour to promote the progression of solid tumours, including breast cancer. We are particularly interested in voltage-gated sodium channels (VGSCs), and their role in regulating membrane electrical activity, adhesion, cellular migration, and invasion. Our current focus is on understanding the mechanisms by which VGSCs regulate the invasion of metastatic breast cancer cells, promoting metastasis. 

Voltage-gated sodium channels and cancer

VGSCs contain a large pore-forming α subunit, together with smaller non-pore-forming β subunits. The β subunits are members of the immunoglobulin superfamily and regulate cell adhesion. VGSC α and β subunits are expressed in a range of different cancers. The Na_v1.5 α subunit is expressed on breast cancer cells, where it enhances migration and invasion, and its expression level associates with poor prognosis in breast cancer patients. We have shown that targeting this channel with antiepileptic drugs reduces tumour growth and metastasis in preclinical models, suggesting that repurposing VGSC-inhibiting medications to cancer may hold promise for reducing metastasis.

Sodium handling and the ionic tumour microenvironment

Aberrant sodium channel/transporter expression in cancer cells may be related to the elevated tissue sodium levels reported in solid tumours, including breast cancer. Using ²³Na-MRI, we have shown that this elevated sodium predominantly resides in the intracellular compartment, suggesting that altered plasma membrane transport routes, including VGSCs, may be an important mechanism underlying sodium accumulation in breast cancer. Using a combination of preclinical in vitro and in vivo models, together with imaging studies in cancer patients, we are currently investigating how expression of these channels is regulated, and the potential utility of altered sodium as a novel imaging biomarker of malignancy.