University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential

Alasmael, N, Mohan, R, Meira, LB, Swales, KE and Plant, NJ (2015) Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential Cancer Letters.

[img]
Preview
Text
Alasmael et al_Cancer Letters_2015.pdf
Available under License : See the attached licence file.

Download (3MB) | Preview
[img]
Preview
Text (licence)
SRI_deposit_agreement.pdf
Available under License : See the attached licence file.

Download (33kB) | Preview

Abstract

Breast cancer is the commonest form of cancer in women, but successful treatment is confounded by the heterogeneous nature of breast tumours: Effective treatments exist for hormone-sensitive tumours, but triple-negative breast cancer results in poor survival. An area of increasing interest is metabolic reprogramming, whereby drug-induced alterations in the metabolic landscape of a tumour slow tumour growth and/or increase sensitivity to existing therapeutics. Nuclear receptors are transcription factors central to the expression of metabolic and transport proteins, and thus represent potential targets for metabolic reprogramming. We show that activation of the nuclear receptor FXR, either by its endogenous ligand CDCA or the synthetic GW4064, leads to cell death in four breast cancer cell lines with distinct phenotypes: MCF-10A (normal), MCF-7 (receptor positive), MDA-MB-231 and MDA-MB-468 (triple negative). Furthermore, we show that the mechanism of cell death is predominantly through the intrinsic apoptotic pathway. Finally, we demonstrate that FXR agonists do not stimulate migration in breast cancer cell lines, an important potential adverse effect. Together, our data support the continued examination of FXR agonists as a novel class of therapeutics for the treatment of breast cancer.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Alasmael, NUNSPECIFIEDUNSPECIFIED
Mohan, RUNSPECIFIEDUNSPECIFIED
Meira, LBUNSPECIFIEDUNSPECIFIED
Swales, KEUNSPECIFIEDUNSPECIFIED
Plant, NJUNSPECIFIEDUNSPECIFIED
Date : 3 November 2015
Identification Number : 10.1016/j.canlet.2015.10.031
Additional Information : Copyright 2015. This manuscript is made available under the CC-BY-NC-ND 4.0 License.
Depositing User : Symplectic Elements
Date Deposited : 12 Nov 2015 11:59
Last Modified : 03 Nov 2016 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/809311

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800