肿瘤坏死因子受体1（TNFR1）通过PIK3CB-p110β调节卵巢癌细胞的致瘤性。

TNFR1 Regulates Ovarian Cancer Cell Tumorigenicity Through PIK3CB-p110Beta.

作者信息

Peng C, Su J, Zeng W, Zhang X, Chen X

机构信息

Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road #87, Changsha, Hunan 410008, China.

出版信息

Curr Mol Med. 2015;15(5):487-96. doi: 10.2174/1566524015666150630125734.

DOI:10.2174/1566524015666150630125734

PMID:26122654

Abstract

Studies have shown that TNFR1 is a key factor in the tumor microenvironment that is dependent on the TNF-α-initiated cascade for tumorigenesis. In this present study, we found that TNFR1 is over-expressed in ovarian cancer, which is relevant to both clinical survival and disease free status. Knockdown of TNFR1 dramatically attenuates malignant phenotypes, including proliferation and colony growth in soft agar, as well as glycolysis in ovarian cancer cells. Unexpectedly, knocking down TNFR1 blocks EGF-induced p-AKT and p-p70S6K expression and EGF-induced cell transformation through PIK3-p110beta rather than p110alpha expression. Taken together, our data provide evidence that TNFR1 plays a critical role in ovarian cancer and show that the EGF induced signaling pathway is independent of the TNF-α triggering cascade signal. Therefore, TNFR1 may serve as a prognostic molecule in ovarian cancer.

摘要

研究表明，肿瘤坏死因子受体1（TNFR1）是肿瘤微环境中的关键因子，其肿瘤发生依赖于肿瘤坏死因子-α（TNF-α）启动的级联反应。在本研究中，我们发现TNFR1在卵巢癌中过度表达，这与临床生存率和无病状态均相关。敲低TNFR1可显著减弱恶性表型，包括软琼脂中的增殖和集落生长，以及卵巢癌细胞中的糖酵解。出乎意料的是，敲低TNFR1可通过PIK3-p110β而非p110α的表达来阻断表皮生长因子（EGF）诱导的磷酸化蛋白激酶B（p-AKT）和磷酸化核糖体蛋白S6激酶（p-p70S6K）的表达以及EGF诱导的细胞转化。综上所述，我们的数据提供了证据表明TNFR1在卵巢癌中起关键作用，并表明EGF诱导的信号通路独立于TNF-α触发的级联信号。因此，TNFR1可能作为卵巢癌的一个预后分子。