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SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity

Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was previously shown to interact with epidermal growth factor receptor (EGFR); the SGLT1–EGFR interaction maintains intracellular glucose levels to promote sur...

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Autores principales: Liu, Huiquan, Ertay, Ayse, Peng, Ping, Li, Juanjuan, Liu, Dian, Xiong, Hua, Zou, Yanmei, Qiu, Hong, Hancock, David, Yuan, Xianglin, Huang, Wei‐Chien, Ewing, Rob M., Downward, Julian, Wang, Yihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717760/
https://www.ncbi.nlm.nih.gov/pubmed/31199048
http://dx.doi.org/10.1002/1878-0261.12530
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author Liu, Huiquan
Ertay, Ayse
Peng, Ping
Li, Juanjuan
Liu, Dian
Xiong, Hua
Zou, Yanmei
Qiu, Hong
Hancock, David
Yuan, Xianglin
Huang, Wei‐Chien
Ewing, Rob M.
Downward, Julian
Wang, Yihua
author_facet Liu, Huiquan
Ertay, Ayse
Peng, Ping
Li, Juanjuan
Liu, Dian
Xiong, Hua
Zou, Yanmei
Qiu, Hong
Hancock, David
Yuan, Xianglin
Huang, Wei‐Chien
Ewing, Rob M.
Downward, Julian
Wang, Yihua
author_sort Liu, Huiquan
collection PubMed
description Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was previously shown to interact with epidermal growth factor receptor (EGFR); the SGLT1–EGFR interaction maintains intracellular glucose levels to promote survival of cancer cells. Here, we explore the role of SGLT1 in triple‐negative breast cancer (TNBC), which is the most aggressive type of breast cancer. We performed TCGA analysis coupled to in vitro experiments in TNBC cell lines as well as in vivo xenografts established in the mammary fat pad of female nude mice. Tissue microarrays of TNBC patients with information of clinical–pathological parameters were also used to investigate the expression and function of SGLT1 in TNBC. We show that high levels of SGLT1 are associated with greater tumour size in TNBC. Knockdown of SGLT1 compromises cell growth in vitro and in vivo. We further demonstrate that SGLT1 depletion results in decreased levels of phospho‐EGFR, and as a result, the activity of downstream signalling pathways (such as AKT and ERK) is inhibited. Hence, targeting SGLT1 itself or the EGFR–SGLT1 interaction may provide novel therapeutics against TNBC.
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spelling pubmed-67177602019-09-04 SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity Liu, Huiquan Ertay, Ayse Peng, Ping Li, Juanjuan Liu, Dian Xiong, Hua Zou, Yanmei Qiu, Hong Hancock, David Yuan, Xianglin Huang, Wei‐Chien Ewing, Rob M. Downward, Julian Wang, Yihua Mol Oncol Research Articles Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was previously shown to interact with epidermal growth factor receptor (EGFR); the SGLT1–EGFR interaction maintains intracellular glucose levels to promote survival of cancer cells. Here, we explore the role of SGLT1 in triple‐negative breast cancer (TNBC), which is the most aggressive type of breast cancer. We performed TCGA analysis coupled to in vitro experiments in TNBC cell lines as well as in vivo xenografts established in the mammary fat pad of female nude mice. Tissue microarrays of TNBC patients with information of clinical–pathological parameters were also used to investigate the expression and function of SGLT1 in TNBC. We show that high levels of SGLT1 are associated with greater tumour size in TNBC. Knockdown of SGLT1 compromises cell growth in vitro and in vivo. We further demonstrate that SGLT1 depletion results in decreased levels of phospho‐EGFR, and as a result, the activity of downstream signalling pathways (such as AKT and ERK) is inhibited. Hence, targeting SGLT1 itself or the EGFR–SGLT1 interaction may provide novel therapeutics against TNBC. John Wiley and Sons Inc. 2019-06-14 2019-09 /pmc/articles/PMC6717760/ /pubmed/31199048 http://dx.doi.org/10.1002/1878-0261.12530 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Liu, Huiquan
Ertay, Ayse
Peng, Ping
Li, Juanjuan
Liu, Dian
Xiong, Hua
Zou, Yanmei
Qiu, Hong
Hancock, David
Yuan, Xianglin
Huang, Wei‐Chien
Ewing, Rob M.
Downward, Julian
Wang, Yihua
SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
title SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
title_full SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
title_fullStr SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
title_full_unstemmed SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
title_short SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
title_sort sglt1 is required for the survival of triple‐negative breast cancer cells via potentiation of egfr activity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717760/
https://www.ncbi.nlm.nih.gov/pubmed/31199048
http://dx.doi.org/10.1002/1878-0261.12530
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