Department of Gastroenterology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Clin Exp Metastasis. 2013 Oct;30(7):933-44. doi: 10.1007/s10585-013-9593-6. Epub 2013 Jun 6.
eEF1A2 is a protein translation factor involved in protein synthesis that is overexpressed in various cancers, with important functions in tumor genesis and progression. We have previously showed that the ectopic expression of eEF1A2 is correlated with lymph node metastasis and perineural invasion in pancreatic cancer. In this study, we investigated the functional role of eEF1A2 in the regulation of cell migration, invasion, and metastasis in pancreatic cancer. Furthermore, we investigated the potential molecular mechanisms involved. By evaluating the invasive ability of a panel of pancreatic cancer cell lines with different metastatic potentials, eEF1A2 expression in cells was positively associated with their invasive ability. The knockdown of eEF1A2 by siRNA decreased the migration and invasion of PANC-1 cells. By contrast, the ectopic expression of exogenous eEF1A2 significantly promoted the migration and invasion of SW1990 cells. Stable eEF1A2 overexpression in a nude mouse model of peritoneal metastasis likewise dramatically enhanced the intraperitoneal metastatic ability of SW1990 cells. In addition, eEF1A2 overexpression could upregulate MMP-9 expression and activity. A significant positive correlation between the overexpression of both eEF1A2 and MMP-9 was observed in pancreatic cancer tissues. The inhibition of MMP-9 activity reduced the promoting effect of eEF1A2 on cell migration and invasion. Furthermore, eEF1A2-mediated cell migration and invasion, as well as MMP-9 expression and upregulation, were largely dependent on the eEF1A2-induced Akt activation. The findings suggested the potentially important role of eEF1A2 in pancreatic cancer migration, invasion, and metastasis. Thus, the results provide evidence of eEF1A2 as a potential therapeutic target in the treatment of aggressive pancreatic cancer.
eEF1A2 是一种参与蛋白质合成的蛋白质翻译因子，在多种癌症中过度表达，在肿瘤发生和进展中具有重要功能。我们之前曾表明，eEF1A2 的异位表达与胰腺癌中的淋巴结转移和神经周围浸润有关。在这项研究中，我们研究了 eEF1A2 在调节胰腺癌细胞迁移、侵袭和转移中的功能作用。此外，我们还研究了涉及的潜在分子机制。通过评估具有不同转移潜力的一系列胰腺癌细胞系的侵袭能力，发现细胞中 eEF1A2 的表达与它们的侵袭能力呈正相关。siRNA 敲低 eEF1A2 可降低 PANC-1 细胞的迁移和侵袭能力。相比之下，外源性 eEF1A2 的异位表达可显著促进 SW1990 细胞的迁移和侵袭。在腹膜转移的裸鼠模型中稳定过表达 eEF1A2 同样显著增强了 SW1990 细胞的腹腔内转移能力。此外，eEF1A2 的过表达可以上调 MMP-9 的表达和活性。在胰腺癌组织中观察到 eEF1A2 和 MMP-9 的过度表达之间存在显著的正相关。抑制 MMP-9 的活性可降低 eEF1A2 对细胞迁移和侵袭的促进作用。此外，eEF1A2 介导的细胞迁移和侵袭以及 MMP-9 的表达和上调在很大程度上取决于 eEF1A2 诱导的 Akt 激活。这些发现表明 eEF1A2 在胰腺癌迁移、侵袭和转移中可能具有重要作用。因此，这些结果为将 eEF1A2 作为治疗侵袭性胰腺癌的潜在治疗靶点提供了证据。
