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

SGLT1 is required for the survival of triple negative breast cancer cells via potentiation of EGFR activity
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 shown to interact with epidermal growth factor receptor (EGFR) and the SGLT1-EGFR interaction maintains the intracellular glucose level 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 clinic-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 the cell growth in vitro and in vivo. We further demonstrate that SGLT1 depletion results in the decreased level 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 EGFR-SGLT1 interaction may provide novel therapeutics against TNBC.
1878-0261
Liu, Huiquan
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Ertay, Ayse
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Peng, Ping
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Li, Juanjuan
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Liu, Dian
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Xiong, Hua
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Zou, Yanmei
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Qiu, Hong
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Hancock, David
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Yuan, Xianglin
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Huang, Wei-Chien
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Ewing, Robert
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Downward, Julian
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Wang, Yihua
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Liu, Huiquan
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Ertay, Ayse
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Peng, Ping
203e2154-9b29-4f23-a8fc-83e9fee85a6d
Li, Juanjuan
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Liu, Dian
ed1f9fa0-33d4-4ff7-a4f3-81036b4ba404
Xiong, Hua
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Zou, Yanmei
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Qiu, Hong
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Hancock, David
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Yuan, Xianglin
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Huang, Wei-Chien
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Ewing, Robert
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Downward, Julian
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Wang, Yihua
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Liu, Huiquan, Ertay, Ayse, Peng, Ping, Li, Juanjuan, Liu, Dian, Xiong, Hua, Zou, Yanmei, Qiu, Hong, Hancock, David, Yuan, Xianglin, Huang, Wei-Chien, Ewing, Robert, Downward, Julian and Wang, Yihua (2019) SGLT1 is required for the survival of triple negative breast cancer cells via potentiation of EGFR activity. Molecular Oncology. (doi:10.1002/1878-0261.12530).

Record type: Article

Abstract

Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was shown to interact with epidermal growth factor receptor (EGFR) and the SGLT1-EGFR interaction maintains the intracellular glucose level 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 clinic-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 the cell growth in vitro and in vivo. We further demonstrate that SGLT1 depletion results in the decreased level 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 EGFR-SGLT1 interaction may provide novel therapeutics against TNBC.

Text
Liu et al Molecular Oncology 2019 - Accepted Manuscript
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Accepted/In Press date: 4 June 2019
e-pub ahead of print date: 14 June 2019

Identifiers

Local EPrints ID: 431477
URI: http://eprints.soton.ac.uk/id/eprint/431477
ISSN: 1878-0261
PURE UUID: 1d157d5a-2dd6-4412-ada5-39e0d502ef09
ORCID for Robert Ewing: ORCID iD orcid.org/0000-0001-6510-4001
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

Catalogue record

Date deposited: 05 Jun 2019 16:30
Last modified: 07 Oct 2020 06:14

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