XB130 mediates cancer cell proliferation and survival through multiple signaling events downstream of Akt.
XB130 mediates cancer cell proliferation and survival through multiple signaling events downstream of Akt.
复制标题
DOI：
10.1371/journal.pone.0043646
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Shiozaki A;Shen-Tu G;Bai X;Iitaka D;De Falco V;Santoro M;Keshavjee S;Liu M
XB130 是一种新型接头蛋白，通过磷脂酰肌醇 3 激酶 (PI3K)/Akt 通路介导 RET/PTC 染色体重排相关的甲状腺癌细胞增殖和存活。最近，在没有 RET/PTC 的情况下，在不同的癌细胞中发现了 XB130。为了确定 XB130 相关癌细胞增殖和存活是否需要 RET/PTC，用 XB130 siRNA 处理 WRO 甲状腺癌细胞（有 RET/PTC 突变）和 A549 肺癌细胞（无 RET/PTC），并检查多个 Akt 下游信号。 XB130 的敲低可抑制 G1-S 期进展，诱导自发性细胞凋亡并增强内在和外在细胞凋亡刺激诱导的细胞死亡。敲低 XB130 会降低 p21Cip1/WAF1、p27Kip1、FOXO3a 和 GSK3β 的磷酸化，增加 p21Cip1/WAF1 蛋白水平以及 caspase-8 和 -9 的裂解。然而，FOXO1 的磷酸化和 p53 的蛋白水平不受 XB130 siRNA 的影响。我们还发现 XB130 可以被多种蛋白酪氨酸激酶磷酸化。这些结果表明XB130是多种蛋白酪氨酸激酶的底物，它可以通过调节PI3K/Akt通路的选定下游信号来调节细胞增殖和存活。 XB130可能参与不同癌细胞的生长和存活。
XB130, a novel adaptor protein, mediates RET/PTC chromosome rearrangement-related thyroid cancer cell proliferation and survival through phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway. Recently, XB130 was found in different cancer cells in the absence of RET/PTC. To determine whether RET/PTC is required of XB130-related cancer cell proliferation and survival, WRO thyroid cancer cells (with RET/PTC mutation) and A549 lung cancer cells (without RET/PTC) were treated with XB130 siRNA, and multiple Akt down-stream signals were examined. Knocking-down of XB130 inhibited G1-S phase progression, and induced spontaneous apoptosis and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Knocking-down of XB130 reduced phosphorylation of p21Cip1/WAF1, p27Kip1, FOXO3a and GSK3β, increased p21Cip1/WAF1protein levels and cleavages of caspase-8 and-9. However, the phosphorylation of FOXO1 and the protein levels of p53 were not affected by XB130 siRNA. We also found XB130 can be phosphorylated by multiple protein tyrosine kinases. These results indicate that XB130 is a substrate of multiple protein tyrosine kinases, and it can regulate cell proliferation and survival through modulating selected down-stream signals of PI3K/Akt pathway. XB130 could be involved in growth and survival of different cancer cells.
登录
查看更多内容
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.8
作者：
Han, B;Bai, XH;Liu, MY
通讯作者：
Liu, MY
DOI：
10.1152/ajplung.00492.2001
发表时间：
2002-08-01
影响因子：
4.9
作者：
Lodyga, M;Bai, XH;Liu, MY
通讯作者：
Liu, MY
影响因子：
4.4
作者：
Han, B;Mura, M;Liu, MY
通讯作者：
Liu, MY
影响因子：
64.5
作者：
GRIECO, M;SANTORO, M;VECCHIO, G
通讯作者：
VECCHIO, G