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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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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