NHERF1 inhibits proliferation of triple-negative breast cancer cells by suppressing GPER signaling.
NHERF1 inhibits proliferation of triple-negative breast cancer cells by suppressing GPER signaling.
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DOI：
10.3892/or.2017.5649
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发表时间：
2017-07
期刊：
影响因子：
4.2
通讯作者：
Yan Wang;Zhiqiang Peng;R. Meng;T. Tao;Qiqi Wang;Chunjuan Zhao;Hua Liu;Ran Song;Junfang Zheng-Ju
中科院分区：
文献类型：
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作者：
Yan Wang;Zhiqiang Peng;R. Meng;T. Tao;Qiqi Wang;Chunjuan Zhao;Hua Liu;Ran Song;Junfang Zheng-Ju
G蛋白偶联雌激素受体（GPER）信号在三阴性乳腺癌（TNBC）中被激活;然而，其调控的详细机制仍不清楚。本研究旨在阐明TNBC中GPER激活的分子机制。在MDA-MB-231细胞（一种TNBC细胞系）中，通过免疫共沉淀和免疫荧光染色测定验证了NHERF 1与GPER的相互作用。在MDA-MB-231细胞中过表达NHERF 1抑制GPER介导的增殖以及ERK 1/2和Akt的磷酸化。此外，NHERF 1表达水平与来自TCGA数据集的TNBC肿瘤早期的GPER激活、ERK 1/2和Akt信号传导以及细胞增殖的基因特征负相关。总之，NHERF 1抑制了GPER介导的信号传导的激活，并抑制了三阴性乳腺癌细胞的增殖。NHERF 1表达的缺失可能在TNBC癌变的早期阶段起关键作用。
G protein-coupled estrogen receptor (GPER) signaling is activated in triple-negative breast cancer (TNBC); however, the detailed mechanisms of its regulation remain unclear. The present study aimed to elucidate the molecular mechanisms involved in GPER activation in TNBC. In MDA-MB-231 cells, a TNBC cell line, NHERF1 interaction with GPER was verified by co-immunoprecipitation and immunofluorescent staining assays. Overexpression of NHERF1 in MDA-MB-231 cells inhibited GPER-mediated proliferation and phosphorylation of ERK1/2 and Akt. Furthermore, NHERF1 expression levels were negatively correlated with the gene signatures of GPER activation, ERK1/2 and Akt signaling, and cell proliferation in early stage of TNBC tumors from the TCGA data set. Taken together, NHERF1 inhibited the activation of GPER-mediated signaling and suppressed the proliferation of triple-negative breast cancer cells. Loss of NHERF1 expression may play a pivotal role in the early stage of TNBC carcinogenesis.