机构:[1]Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China;内科系统肿瘤科(放疗治疗室)重庆医科大学附属第一医院[2]Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, State Key Lab Oncol South China, Canc Epigenet Lab,Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China;其他部门华南肿瘤学国家重点实验室中山大学肿瘤防治中心[3]Chinese Univ Hong Kong, CUHK Shenzhen Res Inst, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China;[4]Suining Ctr Hosp, Dept Oncol, Suining, Peoples R China;[5]Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China;重庆医科大学附属第一医院[6]Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, Dept Clin Oncol, Rm 315, Hong Kong, Hong Kong, Peoples R China
ADAMTS18 dysregulation plays an important role in many disease processes including cancer. We previously found ADAMTS18 as frequently methylated tumor suppressor gene (TSG) for multiple carcinomas, however, its biological functions and underlying molecular mechanisms in breast carcinogenesis remain unknown. Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in 70.8% of tumor tissues by methylation-specific PCR, but none of the normal tissues. Demethylation treatment restored ADAMTS18 expression in silenced breast cell lines. Ectopic expression of ADAMTS18 in breast tumor cells resulted in inhibition of cell migration and invasion. Nude mouse model further confirmed that ADAMTS18 suppressed breast cancer metastasis in vivo. Further mechanistic studies showed that ADAMTS18 suppressed epithelial-mesenchymal transition (EMT), further inhibited migration and invasion of breast cancer cells. ADAMT18 deregulated AKT and NF-kappa B signaling, through inhibiting phosphorylation levels of AKT and p65. Thus, ADAMTS18 as an antimetastatic tumor suppressor antagonizes AKT and NF-kappa B signaling in breast tumorigenesis. Its methylation could be a potential tumor biomarker for breast cancer.
基金:
National Natural Science FoundationNational Natural Science Foundation of China [81372898, 81172582, 31420103915, 81572327]; VC special - Chinese University of Hong Kong
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2017]版:
大类|3 区医学
小类|3 区肿瘤学
最新[2023]版:
大类|2 区医学
小类|3 区肿瘤学
第一作者:
第一作者机构:[1]Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China;
通讯作者:
通讯机构:[1]Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China;[2]Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, State Key Lab Oncol South China, Canc Epigenet Lab,Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China;[3]Chinese Univ Hong Kong, CUHK Shenzhen Res Inst, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China;[5]Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China;[6]Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, Dept Clin Oncol, Rm 315, Hong Kong, Hong Kong, Peoples R China
推荐引用方式(GB/T 7714):
Xu Hongying,Xiao Qian,Fan Yu,et al.Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-kappa B signaling[J].CANCER MEDICINE.2017,6(6):1399-1408.doi:10.1002/cam4.1076.
APA:
Xu, Hongying,Xiao, Qian,Fan, Yu,Xiang, Tingxiu,Li, Chen...&Ren, Guosheng.(2017).Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-kappa B signaling.CANCER MEDICINE,6,(6)
MLA:
Xu, Hongying,et al."Epigenetic silencing of ADAMTS18 promotes cell migration and invasion of breast cancer through AKT and NF-kappa B signaling".CANCER MEDICINE 6..6(2017):1399-1408