机构：[1]Department of Pathology, Affiliated Hospital, Wuxi Medical School, Jiangnan University, Wuxi, China[2]Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA[3]Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China肿瘤专科广东省中医院[4]Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China[5]Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China临床科室其他部门内镜科华南肿瘤学国家重点实验室中山大学肿瘤防治中心[6]Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA[7]Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA[8]Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA[9]Department of Pathology, St Jude Children’s Research Hospital, Memphis, TN 38105, USA[10]Department of Pathology, Medical School, University of Crete, Greece
Our previous studies demonstrated that Jab1/Csn5 overexpression is correlated with low survival rates in cancer patients, including nasopharyngeal carcinoma (NPC), breast cancer and hepatocellular carcinoma, and contributes to NPC's resistance to radiotherapy and cisplatin by regulating DNA damage and repair pathways. However, the molecular mechanism by which Jab1/Csn5 expression is upregulated in NPCs has yet to be determined. In the present study, we identified the upstream regulator of Jab1/Csn5 expression and demonstrated its role in intrinsic resistance of NPC cells to treatment with cisplatin. Signal transducer and activator of transcription-3 (Stat3) expression correlates with and contributes to Jab1/Csn5 transcription. Consistently, silencing of Stat3 in tumors reduced Jab1/Csn5 expression, thereby sensitizing NPC cells to cisplatin-induced apoptosis both in vitro and in vivo. Mechanistically, Stat3 transcriptionally regulated Jab1/Csn5. Furthermore, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer and glioblastoma are associated with significantly shorter survival times from the R2 online database. These findings identify a novel Stat3-Jab1/Csn5 signaling axis in cancer pathogenesis with therapeutic and prognostic relevance.
基金：
National Natural Science Foundation of China [81372816]; Fundamental Research Funds for the Central Universities [JUSRP115A31]; NIH [R01CA90853, P30CA016672]; University Cancer Foundation via the Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center
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外文
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出版当年[2017]版：
大类|1 区医学
小类|1 区遗传学2 区生化与分子生物学2 区细胞生物学2 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|1 区生化与分子生物学1 区遗传学2 区细胞生物学2 区肿瘤学
第一作者：
第一作者机构：[1]Department of Pathology, Affiliated Hospital, Wuxi Medical School, Jiangnan University, Wuxi, China[2]Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
共同第一作者：
通讯作者：
通讯机构：[2]Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA[8]Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA[*1]Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 7435 Fannin Street Unit 950, Houston, TX 77030, USA.
推荐引用方式(GB/T 7714)：
Y Pan,S Wang,B Su,et al.Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression[J].ONCOGENE.2017,36(8):1069-1079.doi:10.1038/onc.2016.271.
APA：
Y Pan,S Wang,B Su,F Zhou,R Zhang...&FX Claret.(2017).Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression.ONCOGENE,36,(8)
MLA：
Y Pan,et al."Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression".ONCOGENE 36..8(2017):1069-1079
医学