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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Main Authors: Huiquan Liu, Ayse Ertay, Ping Peng, Juanjuan Li, Dian Liu, Hua Xiong, Yanmei Zou, Hong Qiu, David Hancock, Xianglin Yuan, Wei‐Chien Huang, Rob M. Ewing, Julian Downward, Yihua Wang
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.12530
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spelling doaj-de56ca1dec634c4eb412a0062a5824e52020-11-25T03:17:13ZengWileyMolecular Oncology1574-78911878-02612019-09-011391874188610.1002/1878-0261.12530SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activityHuiquan Liu0Ayse Ertay1Ping Peng2Juanjuan Li3Dian Liu4Hua Xiong5Yanmei Zou6Hong Qiu7David Hancock8Xianglin Yuan9Wei‐Chien Huang10Rob M. Ewing11Julian Downward12Yihua Wang13Department of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaBiological Sciences, Faculty of Environmental and Life Sciences University of Southampton UKDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaBiological Sciences, Faculty of Environmental and Life Sciences University of Southampton UKDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaOncogene Biology The Francis Crick Institute London UKDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaGraduate Institute of Biomedical Sciences China Medical University Taichung TaiwanBiological Sciences, Faculty of Environmental and Life Sciences University of Southampton UKOncogene Biology The Francis Crick Institute London UKDepartment of Oncology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaSodium/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.https://doi.org/10.1002/1878-0261.12530EGFRSGLT1triple‐negative breast cancer
collection DOAJ
language English
format Article
sources DOAJ
author Huiquan Liu
Ayse Ertay
Ping Peng
Juanjuan Li
Dian Liu
Hua Xiong
Yanmei Zou
Hong Qiu
David Hancock
Xianglin Yuan
Wei‐Chien Huang
Rob M. Ewing
Julian Downward
Yihua Wang
spellingShingle Huiquan Liu
Ayse Ertay
Ping Peng
Juanjuan Li
Dian Liu
Hua Xiong
Yanmei Zou
Hong Qiu
David Hancock
Xianglin Yuan
Wei‐Chien Huang
Rob M. Ewing
Julian Downward
Yihua Wang
SGLT1 is required for the survival of triple‐negative breast cancer cells via potentiation of EGFR activity
Molecular Oncology
EGFR
SGLT1
triple‐negative breast cancer
author_facet Huiquan Liu
Ayse Ertay
Ping Peng
Juanjuan Li
Dian Liu
Hua Xiong
Yanmei Zou
Hong Qiu
David Hancock
Xianglin Yuan
Wei‐Chien Huang
Rob M. Ewing
Julian Downward
Yihua Wang
author_sort Huiquan Liu
title 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_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_sort sglt1 is required for the survival of triple‐negative breast cancer cells via potentiation of egfr activity
publisher Wiley
series Molecular Oncology
issn 1574-7891
1878-0261
publishDate 2019-09-01
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.
topic EGFR
SGLT1
triple‐negative breast cancer
url https://doi.org/10.1002/1878-0261.12530
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