10779/crick.11558184.v1
Huiquan Liu
Huiquan
Liu
Ayse Ertay
Ayse
Ertay
Ping Peng
Ping
Peng
Juanjuan Li
Juanjuan
Li
Dian Liu
Dian
Liu
Hua Xiong
Hua
Xiong
Yanmei Zou
Yanmei
Zou
Hong Qiu
Hong
Qiu
David Hancock
David
Hancock
Xianglin Yuan
Xianglin
Yuan
Wei-Chien Huang
Wei-Chien
Huang
Rob M Ewing
Rob M
Ewing
Julian Downward
Julian
Downward
Yihua Wang
Yihua
Wang
SGLT1 is required for the survival of triple-negative breast cancer cells via potentiation of EGFR activity.
The Francis Crick Institute
2020
EGFR
SGLT1
triple negative breast cancer
triple-negative breast cancer
Downward FC001070
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
2020-01-09 11:42:58
Journal contribution
https://crick.figshare.com/articles/journal_contribution/SGLT1_is_required_for_the_survival_of_triple-negative_breast_cancer_cells_via_potentiation_of_EGFR_activity_/11558184
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 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 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.