SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer.
SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer.
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SHP-1通过与EGFR相互作用作为肿瘤抑制因子并预测人类乳腺癌的预后
DOI：
10.20892/j.issn.2095-3941.2020.0501
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发表时间：
2021-10-01
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
目的：本研究的目的是探讨SHP-1在乳腺癌中的预后价值，其在乳腺癌细胞生长和转移的调节中的作用，以及潜在的机制。研究方法：采用Kaplan-Meier和多因素考克斯回归分析方法，检测160例乳腺癌和160例非乳腺癌组织中SHP-1的表达，并分析其与总生存期的关系。RNA测序数据和SHP-1在乳腺癌中的表达和临床重要性用来自癌症基因组图谱的数据进行评估。通过体外和体内实验研究SHP-1对乳腺癌细胞增殖和侵袭的影响。共聚焦免疫荧光和GST pulldown分析用于证明SHP-1与表皮生长因子受体之间的相互作用，以及其下游途径。采用免疫组化和癌症基因组图谱数据库研究SHP-1和EGFR在人类乳腺癌中的临床相关性。结果如下：SHP-1表达与乳腺癌患者的生存率相关，而SHP-1表达与人类乳腺癌中的EGFR呈负相关。异位SHP-1表达显著抑制乳腺癌细胞增殖、迁移和侵袭。SHP-1敲低诱导更具侵袭性的表型并加速细胞生长。EGFR是一种与SHP-1直接相互作用的蛋白质，其机制介导了SHP-1诱导的Ras/Erk/GSK 3 β信号转导及其下游效应物的失活。结论：SHP-1是乳腺癌患者重要的预后生物标志物，SHP-1-EGFR轴是一个有希望的治疗靶点。
Objective: The aims of this study were to examine the prognostic value of SHP-1 in breast cancer, its roles in the regulation of breast cancer cell growth and metastasis, and the underlying mechanisms. Methods: Tumor specimens from 160 patients with breast cancer and 160 noncancerous tissues were used to examine the expression of SHP-1 and to analyze its association with overall survival through Kaplan–Meier and multivariate Cox regression analyses. RNA sequencing data and the expression and clinical importance of SHP-1 in breast cancer were evaluated with data from The Cancer Genome Atlas. In vitro and in vivo assays were performed to elucidate the effects of SHP-1 on breast cancer cell proliferation and invasion. Confocal immunofluorescence and GST pulldown assays were used to demonstrate the interaction between SHP-1 and epidermal growth factor receptor, as well as its downstream pathways. Immunohistochemistry and The Cancer Genome Atlas database were used to investigate the clinical association between SHP-1 and EGFR in human breast cancer. Results: SHP-1 expression was associated with better survival in patients with breast cancer, whereas SHP-1 expression was negatively correlated with EGFR in human breast cancer. Ectopic SHP-1 expression significantly suppressed breast cancer cell proliferation, migration, and invasion. SHP-1 knockdown induced a more invasive phenotype and accelerated cell growth. Mechanistically, EGFR, a protein directly interacting with SHP-1, mediates the SHP-1-induced inactivation of Ras/Erk/GSK3β signaling and its downstream effectors. Conclusions: SHP-1 is an important prognostic biomarker in patients with breast cancer, and the SHP-1-EGFR axis is a promising target for treatment.