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Tafur et al. J Cancer Metastasis Treat 2019;5:46 Journal of Cancer
DOI: 10.20517/2394-4722.2018.102 Metastasis and Treatment

Original Article Open Access

Differential expression and function of the
endogenous lactate receptor, GPR81, in ERα-

positive/HER2-positive epithelial vs. post-EMT
triple-negative mesenchymal breast cancer cells

Denisse Tafur , Patrick Svrcek , Bruce White 1
1
2
1 Department of Cell Biology, University of Connecticut Health, Farmington, CT 06032, USA.
2 University of Connecticut School of Medicine, University of Connecticut Health, Farmington, CT 06032, USA.
Correspondence to: Dr. Denisse Tafur, the Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
E-mail: denisse.tafur@jax.org
How to cite this article: Tafur D, Svrcek P, White B. Differential expression and function of the endogenous lactate receptor,
GPR81, in ERα-positive/HER2-positive epithelial vs. post-EMT triple-negative mesenchymal breast cancer cells.
J Cancer Metastasis Treat 2019;5:46. http://dx.doi.org/10.20517/2394-4722.2018.102
Received: 20 Dec 2018 First Decision: 11 Feb 2019 Revised: 26 Mar 2019 Accepted: 5 May 2019 Published: 6 Jun 2019

Science Editor: Rafat A. Siddiqui Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: Lactate can signal through the endogenous lactate receptor, GPR81, which is expressed in some cancers.
Lactate metabolism is altered by the metastasis-promoting process of epithelial-mesenchymal transition (EMT).
This study examined the expression and function of GPR81 in breast cancer samples, and in receptor-positive
epithelial vs. triple-negative post-EMT mesenchymal breast cancer cells.

Methods: GPR81 mRNA expression was examined by breast cancer microarray, and by a Kaplan-Meier survival
curve. Using 3-dimensional culture conditions, GPR81 mRNA expression in epithelial and mesenchymal breast
cancer cell lines was measured by qRT-PCR. GPR81 siRNA was used to assess the role of GPR81, alone or in
conjunction with tamoxifen, in the regulation of MCT1 and MCT4 lactate transporters, intracellular lactate, and
cell proliferation and survival.

Results: GPR81 mRNA levels were elevated in receptor-positive breast cancer, relative to non-tumor and triple-
negative samples, and correlated with increased survival. GPR81 expression was elevated in the two epithelial breast
cancer cell lines vs. the corresponding post-EMT mesenchymal cell lines. GPR81 knock-down in epithelial MCF7
cells caused: 1, selectively lower mRNA and protein expression of the MCT1 transporter, but not MCT2 or MCT4

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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