TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway.
TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway.
复制标题
DOI：
10.1186/s12885-022-09386-7
复制
发表时间：
2022-04-07
期刊：
影响因子：
3.8
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Chen L;Qing J;Xiao Y;Huang X;Chi Y;Chen Z
T细胞免疫球蛋白粘蛋白-1（TIM-1）已被报道与几种恶性肿瘤的生物学行为有关;然而，尚不清楚它是否在宫颈癌（CC）中起作用。采用免疫组化、实时荧光定量PCR和Western blotting方法检测宫颈上皮肿瘤组织和细胞中TIM-1的表达。用编码TIM-1的慢病毒载体感染来自表达低水平TIM-1的细胞系的CC细胞。通过CCK-8、伤口愈合、Transwell迁移和侵袭试验以及流式细胞术体外评估CC细胞恶性行为的变化;同时建立异种移植瘤模型以分析TIM-1对体内肿瘤生长的影响。蛋白质印迹法检测细胞周期、细胞凋亡和上皮-间质转化相关蛋白水平的变化。TIM-1在CC组织中的表达高于在高度鳞状上皮内病变、低度鳞状上皮内病变和正常宫颈组织中的表达，并且在三种CC细胞系中也有表达。在HeLa和SiHa细胞中，过度表达TIM-1，增殖，侵袭和迁移增加，而凋亡受到抑制。此外，TIM-1下调p53、BAX和E-cadherin的表达，并增加cyclin D1、Bcl-2、Snail 1、N-cadherin、vimentin、MMP-2和VEGF的表达。PI 3 K、p-AKT和mTOR蛋白水平也增加，而总AKT蛋白水平保持不变。我们的研究表明TIM-1过表达通过调节PI 3 K/AKT/p53和PI 3 K/AKT/mTOR信号通路促进CC细胞的迁移和侵袭，抑制细胞凋亡，可能是CC的一个候选诊断生物标志物。在线版本包含补充材料，可通过10.1186/s12885-022-09386-7获得。
T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). TIM-1 expression in cervical epithelial tumor tissues and cells was detected by immunohistochemistry or real-time quantitative-PCR and western blotting. CC cells from cell lines expressing low levels of TIM-1 were infected with lentiviral vectors encoding TIM-1. Changes in the malignant behavior of CC cells were assessed by CCK-8, wound healing, Transwell migration and invasion assays, and flow cytometry in vitro; while a xenograft tumor model was established to analyze the effects of TIM-1 on tumor growth in vivo. Changes in the levels of proteins related to the cell cycle, apoptosis, and Epithelial-mesenchymal transition (EMT) were determined by western blotting. TIM-1 expression was higher in CC tissues, than in high grade squamous intraepithelial lesion, low grade squamous intraepithelial lesion, or normal cervical tissues, and was also expressed in three CC cell lines. In HeLa and SiHa cells overexpressing TIM-1, proliferation, invasion, and migration increased, while whereas apoptosis was inhibited. Furthermore, TIM-1 downregulated the expression of p53, BAX, and E-cadherin, and increased cyclin D1, Bcl-2, Snail1, N-cadherin, vimentin, MMP-2, and VEGF. PI3K, p-AKT, and mTOR protein levels also increased, while total AKT protein levels remained unchanged. Our study indicated that TIM-1 overexpression promoted cell migration and invasion, and inhibited cell apoptosis in CC through modulation of the PI3K/AKT/p53 and PI3K/AKT/mTOR signaling pathways, and may be a candidate diagnostic biomarker of this disease. The online version contains supplementary material available at 10.1186/s12885-022-09386-7.
登录
查看更多内容
DOI：
10.4049/jimmunol.1001116
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lee HH;Meyer EH;Goya S;Pichavant M;Kim HY;Bu X;Umetsu SE;Jones JC;Savage PB;Iwakura Y;Casasnovas JM;Kaplan G;Freeman GJ;DeKruyff RH;Umetsu DT
通讯作者：
Umetsu DT
影响因子：
--
作者：
Hatok, Jozef;Racay, Peter
通讯作者：
Racay, Peter
影响因子：
34.3
作者：
Arbyn, Marc;Weiderpass, Elisabete;Bray, Freddie
通讯作者：
Bray, Freddie
影响因子：
14.5
作者：
Bourboulia D;Stetler-Stevenson WG
通讯作者：
Stetler-Stevenson WG
影响因子：
8.7
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
通讯作者：
DeKruyff RH