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).
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.
More information
Identifiers
Catalogue record
Export record
Altmetrics
Contributors
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.