Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma

查看全文 作　　者：Yan [1]Liu;Xiaojie [1]Tan;Wenbin [1]Liu;Xi [1]Chen;Xiaomei [1]Hou;Dan [2]Shen;Yibo [1]Ding;Jianhua [1]Yin;Ling [1]Wang;Hongwei [1]Zhang;Yongwei [3]Yu;Jianguo [2]Hou;Timothy [4]C.Thompson;Guangwen [1]Cao

机构地区：[1]Department of Epidemiology,Second Military Medical University,Shanghai 200433,P.R.China;[2]Department of Urology,Changhai Hospital,Second Military Medical University,Shanghai 200433,P.R.China;[3]Department of Pathology,Changhai Hospital,Second Military Medical University,Shanghai 200433,P.R.China;[4]Genitourinary Medical Oncology-Research,University of Texas MD Anderson Cancer Center,Houston,TX 77030,USA

出　　处：《Cancer Communications》索引2018年第38卷第1期,共15页

基　　金：supported by the National Key Basic Research Program(973 program)(2015CB554000 to GC);the National Natural Science Foundation of China(81520108021 and 91529305 to G.C.,81672518 and 81101928 to X.T.);the Three-year Action Plan on Public Health,Phase IV,Shanghai,China(15GWZK0801 to GC). 摘　　要：Background:We previously showed that the expression of follistatin-like protein 1(FSTL1)was significantly down-regulated in metastatic clear-cell renal cell carcinoma(ccRCC).In this study,we aimed to characterize the role of FSTL1 in the development of ccRCC.Methods:The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression.Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown.The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients.Results:FSTL1 knockdown promoted anchorage-independent growth,migration,invasion,and cell cycle of ccRCC cell lines,whereas FSTL1 overexpression attenuated cell migration.FSTL1 knockdown up-regulated nuclear factor-κB(NF-κB)and hypoxia-inducible factor(HIF)signaling pathways,increased epithelial-to-mesenchymal transition,up-regulated interleukin-6 expression,and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor(IκBα)in ccRCC cell lines.FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle,and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues(P<0.001).The mul-tivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325(95%confidence interval 0.118-0.894).HIF-2αexpression was negatively cor-related with FSTL1 expression in ccRCC specimens(r=−0.229,P=0.044).Intratumoral expression of HIF-2α,rather than HIF-1α,significantly predicted an unfavorable prognosis in ccRCC(log-rank,P=0.038).Conclusions:FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2αsignaling pathways.To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC. 关键词：Follistatin-like protein 1 Clear cell renal cell carcinoma NF-κB HIF-2α Prognosis Tumor suppressor

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Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma

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