Li Li Mei
The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016, China.
Inner Mongolia People's HospitalHohhot 010017, China.
Am J Cancer Res. 2018 Mar 1;8(3):551-565. eCollection 2018.
Non-small-cell carcinoma (NSCLC) is one of the most lethal malignancies of lung cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Recent reports show that Golgi membrane protein 1 (GOLM1) is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in NSCLC remain unclear. Herein, we showed that GOLM1 was markedly up-regulated in NSCLC cell lines and clinical tissues. Clinically, NSCLC patients with high expression of GOLM1 had shorter overall survival (OS) and high GOLM1 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis and high tumor stage. Ectopic expression of GOLM1 in NSCLC cells induced epithelial-to-mesenchymal transition (EMT) and promoted proliferation, migration, and invasion of NSCLC cells in vitro. Furthermore, GOLM1 overexpressing significantly promoted the tumorigenicity of NSCLC cells in vivo whereas silencing endogenous GOLM1 caused an opposite outcome. Moreover, we demonstrated that GOLM1 enhanced NSCLC aggressiveness by activating matrix metalloproteinase-13 (MMP13) signaling. Together, our results provided new evidence that GOLM1 overexpression promoted the progression of NSCLC and might represent a novel therapeutic target for its treatment.
非小细胞肺癌（NSCLC）是最致命的肺癌之一，由于缺乏有效的治疗靶点，其预后仍然很差。最近的报告显示，高尔基体膜蛋白1（GOLM1）在多种肿瘤细胞中高表达，作为T细胞的负调节因子，进而促进肿瘤进展。然而，其在NSCLC中的表达和作用仍不清楚。在此我们表明，GOLM1在NSCLC细胞系和临床组织中明显上调。临床上，GOLM1高表达的NSCLC患者总生存期（OS）较短，肿瘤样本中GOLM1高表达与恶性表型显著相关，如淋巴结转移和高肿瘤分期。NSCLC细胞中GOLM1的异位表达诱导上皮-间质转化（EMT），并促进NSCLC细胞在体外增殖、迁移和侵袭。此外，过表达GOLM1在体内显著促进NSCLC细胞的致瘤性，而沉默内源性GOLM1则产生相反的结果。此外，我们证明GOLM1通过激活基质金属蛋白酶-13（MMP13）信号增强NSCLC的侵袭性。总之，我们的结果提供了新的证据，即GOLM1过表达促进NSCLC的进展，可能是其治疗的一个新的治疗靶点。
