GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion
GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion
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DOI：
10.1016/j.bbadis.2019.03.003
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发表时间：
2019-06-01
影响因子：
6.2
通讯作者：
Gomez-Quiroz, Luis E.
中科院分区：
文献类型：
--
作者：
Gerardo-Ramirez, Monserrat;Lazzarini-Lechuga, Roberto;Gomez-Quiroz, Luis E.
尽管在与年龄相关的研究中存在一些争议，但生长分化因子 11 (GDF11) 已被认为是保留严格特征的细胞分化的关键调节因子。 GDF11 在癌症中的研究很少，特别是在那些具有严格能力的癌症中，例如肝细胞癌 (HCC)，这是世界上最具侵袭性的癌症之一。在这里，我们重点研究 GDF11 对肝癌细胞的影响。 GDF11 处理显着减少 HCC 细胞系的增殖、集落和球体形成。治疗 24 小时后，观察到 CDK6、细胞周期蛋白 D1、细胞周期蛋白 A 下调，同时 p27 上调。有趣的是，细胞活力没有改变，但细胞功能受到损害。这些效应可能是由 E-钙粘蛋白和 Occludin 的表达以及 Snail 和 N-钙粘蛋白的抑制以时间依赖性方式诱导的。此外，GDF11处理72小时诱导细胞在没有GDF11的情况下无法维持集落和球体能力长达5天，这表明GDF11对自我更新能力的影响不是暂时的。最后，体内侵袭研究表明，用 GDF11 处理的肝细胞癌细胞的细胞迁移显着减少，这与通过 Ki67 染色判断的增殖减少有关。数据显示，外源性 GDF11 在 HCC 细胞中显示出肿瘤抑制特性。
Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain sternness features, despite some controversies in age-related studies. GDF11 has been poorly investigated in cancer, particularly in those with sternness capacity, such as hepatocellular carcinoma (HCC), one of the most aggressive cancers worldwide. Here, we focused on investigating the effects of GDF11 in liver cancer cells. GDF11 treatment significantly reduced proliferation, colony and spheroid formation in HCC cell lines. Consistently, down-regulation of CDK6, cyclin D1, cyclin A, and concomitant upregulation of p27 was observed after 24 h of treatment. Interestingly, cell viability was unchanged, but cell functionality was compromised. These effects were potentially induced by the expression of E-cadherin and occludin, as well as Snail and N-cadherin repression, in a time-dependent manner. Furthermore, GDF11 treatment for 72 h induced that cells were incapable of sustaining colony and sphere capacity in the absent of GDF11, up to 5 days, indicating that the effect of GDF11 on self-renewal capacity is not transient. Finally, in vivo invasion studies revealed a significant decrease in cell migration of hepatocellular carcinoma cells treated with GDF11 associated to a decreased proliferation judged by Ki67 staining. Data show that exogenous GDF11 displays tumor suppressor properties in HCC cells.