NEDD9 promotes cancer stemness by recruiting myeloid-derived suppressor cells via CXCL8 in esophageal squamous cell carcinoma

作     者：Dongli Yue Shasha Liu Tengfei Zhang Yong Wang Guohui Qin Xinfeng Chen Huanyu Zhang Dong Wang Lan Huang Feng Wang Liping Wang Song Zhao Yi Zhang Dongli Yue;Shasha Liu;Tengfei Zhang;Yong Wang;Guohui Qin;Xinfeng Chen;Huanyu Zhang;Dong Wang;Lan Huang;Feng Wang;Liping Wang;Song Zhao;Yi Zhang

作者机构：Biotherapy Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Cancer Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular OncologyNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)Beijing 100730China Biomed Innovation CenterYehoo GroupShenzhen 518067China Department of Thoracic Surgerythe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China School of Life SciencesZhengzhou UniversityZhengzhou 450052China Henan Key Laboratory for Tumor Immunology and BiotherapyZhengzhou 450052China 

出 版 物：《Cancer Biology & Medicine》 (癌症生物学与医学（英文版）)

年 卷 期：2021年第18卷第3期

页      面：705-720页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(Grant Nos.81602599,31400752,81771781,and U1804281) the National Key Research and Development Program of China(Grant No.2016YFC1303501) 

主　　题：Esophageal squamous cell carcinoma(ESCC) cancer stem cells(CSCs) neural precursor cell expressed,developmentally downregulated 9(NEDD9) myeloid derived suppressor cells(MDSCs) 

摘      要：Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates *** stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy and radiotherapy ***-derived suppressor cells(MDSCs),in contrast,are known to be involved in mediating ***,we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor ***:ESCC tissues and cell lines were *** precursor cell expressed,developmentally downregulated 9(NEDD9)was knocked down and overexpressed by lentiviral *** PCR,Western blot,immunohistochemistry,cell invasion,flow cytometry,cell sorting,multiplex chemokine profiling,and tumor growth analyses were ***:Microarray analysis revealed 10 upregulated genes in esophageal *** NEDD9 was upregulated in CSCs using the sphere-forming ***9 expression was correlated with tumor invasion(P=0.0218),differentiation(P=0.0153),and poor prognosis(P=0.0373).Additionally,NEDD9 was required to maintain the stem-like *** of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8(CXCL8)expression via the ERK ***8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in *** promoted the stemness of ESCC cells through NEDD9 via the Notch ***:As a marker of ESCC,NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor,suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.