A role for TXNIP in cancer progression.
PhD project (3/4 yr research project leading to independent research at the doctorate level)
Jeff Holly, Claire Perks, Nic Timpson
Among the genes identified from recent epigenome wide association studies (EWAS) of Type II diabetes was thioredoxin interacting protein (TXNIP). TXNIP was also identified in an EWAS of lipid profiles. Although TXNIP was originally characterised as an inhibitor of thioredoxin it has subsequently been shown to be a critical regulator of cell metabolism independent of its interaction with thioredoxin. TXNIP is a member of the alpha-arrestin family of cell receptor regulators that has an important role in cell metabolism at least in part via regulation of the PI3K pathway and the uptake and metabolism of glucose. These metabolic pathways are also critical for the progression of epithelial cancers such as those of the breast, prostate and colorectum.
Aims & objectives
An interdisciplinary project to investigate the role of TXNIP in cell metabolism and in the progression of breast, prostate and colorectal cancers examining both cell models and tumour specimens from patients. In populations the causal effects of epigenetic variance and heritable traits in the TXNIP (and associated pathways identified in the cell biology) will be examined in relation to the risk and progression of these cancers.
A range of cell lines including those from breast, prostate and colorectal cancers will be employed to examine the effects of manipulations of TXNIP expression. Cell growth, metabolism, differentiation status, invasion and migration will be examined using established assays. PCR and western blotting will be used to monitor abundance of mRNA and protein respectively and associations between molecules will be examined using immunoprecipitation. Associations between genetic and epigenetic variants in TXNIP and associated pathways will be examined in large cohorts and in data from the UK Biobank.
Created on Dec. 16, 2016, 11:17 a.m.