Department of Radiation Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
Department of Respiratory medicine, The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,510260, China.
Int J Biochem Cell Biol. 2018 Jan;94:98-106. doi: 10.1016/j.biocel.2017.12.002. Epub 2017 Dec 5.
ELF3 is one of the member of transcription factors from E-twenty-six family, its role varies in different types of cancer. However, the role and specific mechanisms of ELF3 in the development of non-small cell lung cancer (NSCLC) still remains largely unknown. In our study, ELF3 was observed to be upregulated in NSCLC tissues compared to the corresponding normal lung tissue at mRNA and protein levels, and its expression level was correlated with the overall survival of patients with NSCLC. Silencing of the ELF3 gene in NSCLC cells inhibited the proliferation and metastasis significantly in vitro and in vivo. Conversely, overexpression of ELF3 in NSCLC cells promoted cancer growth and metastasis in vitro. Mechanistically, ELF3 activated PI3K/AKT and ERK signaling pathways and its downstream effectors, thus regulating the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, the promotive effects of ELF3 on cellular proliferation and metastasis could be rescued by Ly294002 (inhibitor of PI3K) and U0126 (inhibitor of MEK1/2). The results show that ELF3 promotes cell growth and metastasis by regulating PI3K/Akt and ERK pathways in NSCLC and that it may be a promising new target for the treatment of NSCLC patients.
ELF3 是 E 区二十六个转录因子家族的成员之一，其在不同类型的癌症中的作用各不相同。然而，ELF3 在非小细胞肺癌（NSCLC）发展中的作用和具体机制在很大程度上仍然未知。在我们的研究中，与相应的正常肺组织相比，ELF3 在 NSCLC 组织中在 mRNA 和蛋白质水平上均上调，并且其表达水平与 NSCLC 患者的总生存率相关。在 NSCLC 细胞中沉默 ELF3 基因可显著抑制体外和体内的增殖和转移。相反，ELF3 在 NSCLC 细胞中的过表达可促进体外的肿瘤生长和转移。从机制上讲，ELF3 激活了 PI3K/AKT 和 ERK 信号通路及其下游效应物，从而调节细胞周期和上皮-间充质转化（EMT）。此外，LY294002（PI3K 抑制剂）和 U0126（MEK1/2 抑制剂）可挽救 ELF3 对细胞增殖和转移的促进作用。结果表明，ELF3 通过调节 NSCLC 中的 PI3K/Akt 和 ERK 通路促进细胞生长和转移，它可能是治疗 NSCLC 患者的有前途的新靶标。
