SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer  

作　　者：Qian Geng Ruiting Xian Yinjue Yu Fengsheng Chen Rong Li 

机构地区：[1]Department of Oncology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [2]Cancer Center,the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University,Changzhou 213003,China [3]Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510315,China

出　　处：《Cancer Biology & Medicine》2022年第4期468-485,共18页癌症生物学与医学（英文版）

基　　金：This project was supported by the National Natural Science Foundation of China(Grant No.81772822);the Natural Science Foundation of Guangdong Province(Grant No.2017A030313540);the Changzhou Health and Family Planning Commission(Grant No.ZD201711);the Young Scientists Foundation of Changzhou No.2 People’s Hospital(Grant No.2018K004).

摘　　要：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/GSK3βsignaling 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.

关 键 词：SHP-1 EGFR breast cancer PROLIFERATION migration 

分 类 号：R737.9[医药卫生—肿瘤]