TNF antagonizes CCN1 in apoptosis in esophageal adenocarcinoma
TNF antagonizes CCN1 in apoptosis in esophageal adenocarcinoma
复制标题
DOI：
10.1016/j.cyto.2021.155728
复制
发表时间：
2021-10-08
期刊：
影响因子：
3.8
通讯作者：
Chai, Jianyuan
中科院分区：
文献类型：
--
作者：
Dang, Tong;Chang, Zhiheng;Chai, Jianyuan
TNF信号传导主要通过激活NF κ B来支持细胞生长，并且仅在NF κ B激活失败时诱导细胞死亡。CCN 1是一种基质细胞蛋白，已报道其能够将TNF从促存活因子转化为细胞死亡的刺激物而不干扰NF κ B信号传导。在这项研究中，我们研究了CCN 1和TNF在食管腺癌背景下的关系，发现CCN 1并没有帮助TNF诱导细胞死亡时，他们在一起，相反，它抑制TNF的表达，以及TNF诱导的JNK激活和凋亡。CCN 1通过上调TRAIL及其死亡受体诱导癌细胞凋亡。TNF的存在显著降低CCN 1的表达及其诱导凋亡的能力。此外，我们发现CCN 1通过ITGA 11增强ADAM 17介导的TNF受体切割，并且该作用产生的可溶性诱饵受体中和了TNF活性。总之，CCN 1和TNF在食管癌细胞中相互拮抗。
TNF signaling mostly supports cell growth by activating NF kappa B and only induces cell death when NF kappa B activation fails. CCN1 is a matricellular protein that has been reported capable to convert TNF from a pro-survival factor into a stimulus for cell death without interfering with NF kappa B signaling. In this study, we examined the relationship between CCN1 and TNF in the context of esophageal adenocarcinoma and found that CCN1 did not help TNF to induce cell death when they were together, instead, it inhibited TNF expression, as well as TNF-induced JNK activation and apoptosis. CCN1 induced apoptosis in the cancer cells by itself through upregulation of TRAIL and its death receptors. The presence of TNF significantly lowered CCN1 expression and its capability in apoptosis induction. Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.