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.

中文翻译：

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SGLT1 通过增强 EGFR 活性来维持三阴性乳腺癌细胞的存活。


钠/葡萄糖协同转运蛋白 1 (SGLT1) 是一种必需的活性葡萄糖转运蛋白，有助于维持高细胞内葡萄糖水平，之前已被证明与表皮生长因子受体 (EGFR) 相互作用； SGLT1-EGFR 相互作用维持细胞内葡萄糖水平以促进癌细胞的存活。在这里，我们探讨了 SGLT1 在三阴性乳腺癌 (TNBC) 中的作用，这是最具侵袭性的乳腺癌类型。我们将 TCGA 分析与 TNBC 细胞系的体外实验以及雌性裸鼠乳腺脂肪垫中建立的体内异种移植物结合起来进行。具有临床病理参数信息的 TNBC 患者的组织微阵列也用于研究 SGLT1 在 TNBC 中的表达和功能。我们发现，高水平的 SGLT1 与 TNBC 中较大的肿瘤大小相关。 SGLT1 的敲低会损害细胞在体外和体内的生长。我们进一步证明，SGLT1 缺失会导致磷酸 EGFR 水平降低，从而抑制下游信号通路（例如 AKT 和 ERK）的活性。因此，靶向 SGLT1 本身或 EGFR-SGLT1 相互作用可能提供针对 TNBC 的新疗法。