Department of Pathology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA, USA.
Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
J Cell Mol Med. 2021 Mar;25(6):2795-2805. doi: 10.1111/jcmm.16307. Epub 2021 Feb 4.
Although the Eukaryotic Translation Initiation Factor 4 Gamma 1 (EIF4G1) has been found overexpressed in a variety of cancers, its role in non-small cell lung cancers (NSCLC) pathogenesis especially in immunoregulatory functions, its clinical relevance and therapeutic potential remain largely unknown. By using cancer patients tissue assays, the results indicate that EIF4G1 expressional levels are much higher in NSCLC tissues than in adjacent or normal lung tissues, which are also associated with NSCLC patient survival. By using an RNA-Sequencing based pipeline, the data show that EIF4G1 has a significant association with immune checkpoint molecules such as PD-1/PD-L1 in NSCLC. EIF4G1 small-molecule inhibitors effectively repress NSCLC growth in cell culture and xenograft animal models. Protein array results identify the signature of proteins controlled by EIF4G1 in NSCLC cells, in which new candidates such as MUC1 and NRG1 are required for NSCLC survival and tumorigenesis with clinical relevance. Taken together, these results have for the first time demonstrated the immunoregulatory functions, clinical relevance and therapeutic potential of the EIF4G1 network in NSCLC, which may represent a promising and novel target to improve lung cancer treatment.
虽然真核翻译起始因子 4 伽马 1（EIF4G1）在多种癌症中被发现过度表达，但它在非小细胞肺癌（NSCLC）发病机制中的作用，特别是在免疫调节功能方面，其临床相关性和治疗潜力在很大程度上仍然未知。通过使用癌症患者组织分析，结果表明 EIF4G1 在 NSCLC 组织中的表达水平明显高于相邻或正常肺组织，这也与 NSCLC 患者的生存相关。通过使用基于 RNA 测序的流水线，数据表明 EIF4G1 与 NSCLC 中的免疫检查点分子如 PD-1/PD-L1 有显著关联。EIF4G1 小分子抑制剂可有效抑制 NSCLC 细胞在细胞培养和异种移植动物模型中的生长。蛋白质阵列结果确定了 EIF4G1 在 NSCLC 细胞中控制的蛋白质特征，其中新的候选物如 MUC1 和 NRG1 是 NSCLC 生存和肿瘤发生所必需的，具有临床相关性。总之，这些结果首次证明了 EIF4G1 网络在 NSCLC 中的免疫调节功能、临床相关性和治疗潜力，这可能代表改善肺癌治疗的一个有前途和新颖的目标。
