Tg737 signaling is required for hypoxia-enhanced invasion and migration of hepatoma cells.
Tg737 signaling is required for hypoxia-enhanced invasion and migration of hepatoma cells.
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Tg737信号传导是缺氧增强肝癌细胞侵袭和迁移所必需的
DOI：
10.1186/1756-9966-31-75
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发表时间：
2012-09-13
期刊：
影响因子：
--
通讯作者：
Tao K
中科院分区：
文献类型：
--
作者：
You N;Liu W;Tang L;Zhong X;Ji R;Zhang N;Wang D;He Y;Dou K;Tao K
背景虽然缺氧可以促进肝癌细胞的侵袭和迁移，但其分子机制尚不清楚。我们以前的研究表明，Tg 737的损失与肝癌细胞的侵袭和迁移，因此，我们假设，Tg 737信号可能需要缺氧增强的侵袭和migration.MethodsWe建立在体外常氧或缺氧模型，探讨Tg 737在缺氧增强的肝癌细胞的侵袭和迁移的作用。将肝癌细胞系HepG 2和MHCC 97-H置于常氧或低氧条件下，检测细胞粘附、侵袭和迁移能力。用Western blot检测常氧或缺氧条件下Tg 737的表达;用流式细胞术测定细胞活力。此外，我们建立了HepG 2和MHCC 97-H细胞，在缺氧下孵育之前过表达Tg 737，并研究了它们的转移特性。最后，我们分析了参与的关键分子事件，已知调节侵袭和migration.ResultsIn这项研究中，Tg 737的表达显着抑制HepG 2和MHCC 97-H细胞暴露于缺氧。Tg 737表达的下调对应于显著降低的粘附和增加的侵袭和迁移。缺氧还降低了多囊蛋白-1的表达/分泌，增加了白细胞介素-8（IL-8）的分泌，并增加了活性和总转化生长因子β 1（TGF-β1）的水平，TGF-β1是细胞侵袭和迁移的关键调节因子。此外，pcDNA3.1-Tg 737转染前缺氧处理的肝癌细胞的侵袭能力和迁移能力的降低和增加减弱。结论Tg 737可能通过多囊蛋白1、IL-8和TGF-β1途径参与低氧诱导的细胞侵袭和迁移。总之，这项工作表明，Tg 737参与了缺氧条件下肝癌细胞的侵袭和迁移，并参与了多囊蛋白-1，IL-8和TGF-β1信号通路。TG 737是一个潜在的治疗靶点，用于抑制肝癌细胞在缺氧区域的高侵袭和迁移潜力。
BackgroundAlthough hypoxia is known to promote hepatoma cell invasion and migration, little is known regarding the molecular mechanisms of this process. Our previous research showed that loss of Tg737 is associated with hepatoma cell invasion and migration; therefore, we hypothesized that the Tg737 signal might be required for hypoxia-enhanced invasion and migration.MethodsWe established in vitro normoxic or hypoxic models to investigate the role of Tg737 in the hypoxia-enhanced invasion and migration of hepatoma cells. The hepatoma cell lines HepG2 and MHCC97-H were subjected to normoxic or hypoxic conditions, and the cell adhesion, invasion, and migration capabilities were tested. The expression of Tg737 under normoxia or hypoxia was detected using western blot assays; cell viability was determined using flow cytometry. Furthermore, we created HepG2 and MHCC97-H cells that over expressed Tg737 prior to incubation under hypoxia and investigated their metastatic characteristics. Finally, we analyzed the involvement of critical molecular events known to regulate invasion and migration.ResultsIn this study, Tg737 expression was significantly inhibited in HepG2 and MHCC97-H cells following exposure to hypoxia. The down regulation of Tg737 expression corresponded to significantly decreased adhesion and increased invasion and migration. Hypoxia also decreased the expression/secretion of polycystin-1, increased the secretion of interleukin-8 (IL-8), and increased the levels of active and total transforming growth factor β 1 (TGF-β1), critical regulators of cell invasion and migration. Moreover, the decrease in adhesiveness and the increase in the invasive and migratory capacities of hypoxia-treated hepatoma cells were attenuated by pcDNA3.1-Tg737 transfection prior to hypoxia. Finally, following the up regulation of Tg737, the expression/secretion of polycystin-1 increased, and the secretion of IL-8 and the levels of active and total TGF-β1 decreased correspondingly.ConclusionsThese data provide evidence that Tg737 contributes to hypoxia-induced invasion and migration, partially through the polycystin-1, IL-8, and TGF-β1 pathway. Taken together, this work suggests that Tg737 is involved in the invasion and migration of hepatoma cells under hypoxia, with the involvement of the polycystin-1, IL-8, and TGF-β1 signaling pathway. Tg737 is a potential therapeutic target for inhibiting the high invasion and migration potential of hepatoma cells in hypoxic regions.
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