S100A8 promotes epithelial-mesenchymal transition and metastasis under TGF-β/USF2 axis in colorectal cancer

作     者：Si Li Jun Zhang Senmi Qian Xuesong Wu Liang Sun Tianyi Ling Yao Jin Wenxiao Li Lichao Sun Maode Lai Fangying Xu 

作者机构：Department of Pathology and Pathophysiologyand Department of General Surgery of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058P.R.China Department of Pathology and PathophysiologyZhejiang University School of MedicineHangzhouZhejiang 310058P.R.China Key Laboratory of Disease Proteomics of Zhejiang ProvinceZhejiang University School of MedicineHangzhouZhejiang 310058P.R.China State Key Laboratory of Molecular OncologyNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China 

出 版 物：《Cancer Communications》 (癌症通讯（英文）)

年 卷 期：2021年第41卷第2期

页      面：154-170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：This work was supported by the grants of the National Natural Science Foundation of China(81772570) the Open Projects of State Key Laboratory of Molecular Oncology(SKL-KF-2019-17) the Program of Introducing Talents of Discipline to Universities(B13026) 

主　　题：colorectal cancer epithelial-mesenchymal transition metastasis prognosis transforming growth factor-β upstream transcription factor 2 S100 calcium-binding protein A8 

摘      要：Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and ***,the regulatory mechanism of TGF-βin inducing EMT in colorectal cancer(CRC)has not been fully *** previous studies,it was found that S100A8 may regulate *** study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in ***:S100A8 and upstream transcription factor 2(USF2)expression was detected by immunohistochemistry in 412 CRC ***-Meier survival analysis was *** vitro,Western blot,and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced *** metastasis models were used to determine in vivo metastasis *** reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 ***:During TGF-β-induced EMT in CRC cells,S100A8 and the transcription factor USF2 were upregulated.S100A8 promoted cell migration and invasion and ***2 transcriptionally regulated S100A8 expression by directly binding to its promoter ***,TGF-βenhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells.S100A8 expression in tumor cells was associated with poor overall survival in ***2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal ***:TGF-βwas found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 ***2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.