Group: Nutrition and Cancer, School of Food Science and Nutrition, Faculty of Environment, University of Leeds, Leeds, UK

Key members: James L Thorne, Giorgia Cioccoloni, Mengfan Xu, Emtenan Jefrei.

Contact: James L Thorne 
 
Our research is focused on oxysterols signalling in cancer. The liver x receptor is a member of the ligand activated nuclear receptor (NR) superfamily of transcription factors. Our recent discoveries have indicated that oxysterol signalling is a novel therapeutic target in cancer. For example, the oxysterol-LXR pathway drives chemotherapy resistance in aggressive ‘triple negative’ breast cancer (1) but actually, the intra-tumour concentration of oxysterols are quite similar between different breast cancer subtypes (2). This prompted us to examine the underpinning molecular mechanisms. We discovered several novel LXR splice variants that linked to patient prognosis (3) and that in TNBC, activity of the LXR pathway is enhanced compared to other breast cancer subtypes due to loss of corepressor activity (4). Therapeutically, we found that phytosterols can interfere with oxysterol signalling in breast cancer (5) and that they may prevent cancer progression (6). Drugs that impair oxysterol and cholesterol esterification enzymes are also of interest as they may reduce severity of several cancers (7).

We often have openings for PhD students to join us, so and for current information on opportunities in this group, please visit https://environment.leeds.ac.uk/food-nutrition/staff/7156/dr-james-l-thorne
 
Key papers for ENOR: 

1.    Hutchinson SA, Websdale A, Cioccoloni G, Roberg-Larsen H, Lianto P, Kim B, et al. Liver x receptor alpha drives chemoresistance in response to side-chain hydroxycholesterols in triple negative breast cancer. Oncogene 2021;40:2872-83
2.    Solheim S, Hutchinson SA, Lundanes E, Wilson SR, Thorne JL, Roberg-Larsen H. Fast liquid chromatography-mass spectrometry reveals side chain oxysterol heterogeneity in breast cancer tumour samples. J Steroid Biochem Mol Biol 2019
3.    Lianto P, Hutchinson SA, Moore JB, Hughes TA, Thorne JL. Characterization and prognostic value of LXR splice variants in triple-negative breast cancer. iScience 2021;24:103212
4.    Hutchinson SA, Lianto P, Roberg-Larsen H, Battaglia S, Hughes TA, Thorne JL. ER-Negative Breast Cancer Is Highly Responsive to Cholesterol Metabolite Signalling. Nutrients 2019;11
5.    Hutchinson SA, Lianto P, Moore JB, Hughes TA, Thorne JL. Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells. Int J Mol Sci 2019;20
6.    Cioccoloni G, Soteriou C, Websdale A, Wallis L, Zulyniak MA, Thorne JL. Phytosterols and phytostanols and the hallmarks of cancer in model organisms: A systematic review and meta-analysis. Crit Rev Food Sci Nutr 2022;62:1145-65
7.    Websdale A, Kiew Y, Chalmers P, Chen X, Cioccoloni G, Hughes TA, et al. Pharmacologic and genetic inhibition of cholesterol esterification enzymes reduces tumour burden: A systematic review and meta-analysis of preclinical models. Biochem Pharmacol 2022;196:114731