Human tumor necrosis factor alpha-induced protein eight-like 1 exhibited potent anti-tumor effect through modulation of proliferation, survival, migration and invasion of lung cancer cells
Human tumor necrosis factor alpha-induced protein eight-like 1 exhibited potent anti-tumor effect through modulation of proliferation, survival, migration and invasion of lung cancer cells
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DOI：
10.1007/s11010-021-04060-1
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发表时间：
2021-04-25
影响因子：
4.3
通讯作者：
Kunnumakkara, Ajaikumar B.
中科院分区：
文献类型：
--
作者：
Bordoloi, Devivasha;Padmavathi, Ganesan;Kunnumakkara, Ajaikumar B.
肺癌是全球最常见的肿瘤之一。吸烟、接触不同的职业和环境致癌物以及各种饮食因素与肺癌的发生密切相关。肺癌的5年生存率极低，这可归因于其早期扩散倾向、缺乏适当的生物标志物和针对这种侵袭性肿瘤的适当治疗策略。新的证据表明，肿瘤坏死因子-α 诱导的蛋白 8 样 1（TIPE1 或 TNFAIP8L1）作为细胞死亡调节因子，作为重要的生物标志物具有很高的前景。有趣的是，与正常肺组织相比，这种蛋白质在人类肺癌组织中显着下调。此外，该蛋白在肺肿瘤的不同阶段和级别中均表现出显着的下调。进一步敲除 TIPE1 可通过调节 Akt/mTOR/STAT-3 信号级联增强 NCIH460 人肺癌细胞的增殖、存活、迁移和侵袭。此外，TIPE1被发现通过增强肺癌细胞的增殖、存活和迁移而参与尼古丁、4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮、N-亚硝基降烟碱和苯并[a]芘介导的肺癌。总而言之，这种新发现的蛋白质在肺癌发病机制中发挥着关键作用，并具有作为有效管理这种侵袭性肿瘤的重要工具的巨大前景。
Lung cancer represents one of the most prevalent neoplasms across the globe. Tobacco smoking, exposure to different occupational and environmental carcinogens, and various dietary factors are strongly implicated in the development of lung cancer. The 5-year survival rate of lung cancer is extremely poor which can be attributed to its propensity for early spread, lack of appropriate biomarkers and proper therapeutic strategies for this aggressive neoplasm. Emerging evidence suggests tumor necrosis factor-alpha-induced protein eight like 1 (TIPE1 or TNFAIP8L1), which functions as a cell death regulator, to hold high prospect as an important biomarker. Interestingly, this protein was found to be significantly downregulated in human lung cancer tissues compared to normal lung tissues. In addition, this protein exerted marked downregulation in different stages and grades of lung tumor. Further knockout of TIPE1 led to the enhancement in proliferation, survival, migration and invasion of NCIH460 human lung cancer cells through modulation of Akt/mTOR/STAT-3 signaling cascade. In addition, TIPE1 was found to be involved in nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosonornicotine and benzo[a]pyrene-mediated lung cancer through enhanced proliferation, survival and migration of lung cancer cells. Altogether, this newly identified protein plays a critical role in lung cancer pathogenesis and possess enormous prospect to serve as an important tool in the effective management of this aggressive neoplasm.