蛋白激酶B
卵巢癌
激酶
MAPK/ERK通路
癌症研究
基因敲除
生物
蛋白激酶A
下调和上调
PI3K/AKT/mTOR通路
癌细胞
免疫沉淀
细胞生物学
分子生物学
化学
癌症
信号转导
细胞培养
生物化学
基因
遗传学
作者
Bianhua Shi,Jiayu Bao,Yongbin Liu,Juan Shi
出处
期刊:FEBS Open Bio
[Wiley]
日期:2018-07-14
卷期号:8 (9): 1497-1507
被引量:19
标识
DOI:10.1002/2211-5463.12492
摘要
The expression of death receptor 6 ( DR 6) is abnormal in some cancer types, but the function and underlying molecular mechanisms of DR 6 in tumor progression are not yet clear. In the present study, our analysis of ovarian cancer RNA sequencing data from The Cancer Genome Atlas revealed that DR 6 is upregulated in human ovarian cancer. We confirmed that the expression level of DR 6 is upregulated in ovarian cancer tissues when compared with matched adjacent normal tissues. In addition, DR 6 enhanced ovarian carcinoma cell migration ability, and decreased expression of DR 6 inhibited the expression of matrix metalloprotease ( MMP ) 2 and MMP 9, and increased the expression of E‐cadherin. Additionally, DR 6 sh RNA caused a significant decrease in phosphoinositide‐3‐kinase ( PI 3K), phospho (p) ‐ AKT , p‐extracellular signal‐regulated kinase ( ERK ), and p‐mitogen‐activated protein kinase kinase expression in SKOV 3 cells. These results suggested that DR 6 can enhance ovarian carcinoma cell migration ability through the mitogen‐activated protein kinase/ ERK and PI 3K/ AKT pathways. Notably, mass spectrometric analysis indicated that DR 6 co‐purified with kinesin family member 11 ( KIF 11), and we verified the interaction between KIF 11 and DR 6 by co‐immunoprecipitation and glutathione S ‐transferase pull‐down. Furthermore, we demonstrated that DR 6 can bind tumor necrosis factor receptor‐associated factor 4 ( TRAF 4) with co‐immunoprecipitation. Overexpression of KIF 11 or TRAF 4 eliminated the suppression of carcinoma cell migration by DR 6 knockdown. We also found that TRAF 4 and KIF 11 were upregulated in ovarian carcinomas and that their level of expression was positively correlated with that of DR 6. The findings above suggest that DR 6 may play a notable oncogenic role in ovarian malignancy by interacting with TRAF 4 and KIF 11, and that DR 6 may be an effective therapeutic target in ovarian cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI