内质网金属肽酶1(ERMP1)参与细胞对氧化应激的反应。然而，它在癌细胞增殖和进展中的功能角色尚不清楚。本研究的重点是探讨ERMP1在正常和环境应激条件下调节结直肠癌（CRC）细胞增殖和进展的分子机制。在这个实验研究中，使用逆转录定量聚合酶链反应（RT-qPCR）评估了CRC细胞中ERMP1的表达。使用对HCT116细胞进行植入ERMP1特异性shRNA的慢病毒载体编码，降低了ERMP1的表达。使用通过脂质体转染方法将ERMP1过表达质粒转染入SW48细胞来上调ERMP1。为了评估ERMP1在细胞和环境应激条件下的作用，将降低ERMP1表达的细胞暴露于饥饿、无血清培养基以及红氧化剂或化疗药物处理72小时的应激条件中。通过Western blotting评估AKT、p-AKT、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）、β-连环蛋白、p-β-连环蛋白、E-钙粘蛋白和葡萄糖调节蛋白78(GRP78)的表达。通过RT-qPCR评估ERMP1、CYCLIN D和c-MYC的表达。通过流式细胞术确定GRP78的细胞表面定位、细胞周期分布和凋亡。ERMP1的敲减减少了细胞增殖，使PI3K/AKT途径失活，促使G1阻滞，并减弱了自由β-连环蛋白和CYCLIN D的表达。ERMP1过表达细胞则得到相反的结果。ERMP1的敲减也减少了GRP78在细胞表面的定位。不同的环境应激条件对ERMP1下调的细胞产生不同的影响。ERMP1在CRC细胞中作为一个致癌基因通过促进恶性特性发挥作用。磷脂酰肌醇3-激酶（PI3K）/AKT/β-连环蛋白途径和GRP78的定位与ERMP1的效应密切相关。因此，ERMP1可能被视为与CRC相关的治疗策略中的一个有前景的靶点。

Endoplasmic reticulum-metallopeptidase 1 (ERMP1) is involved in cellular response to oxidative stress. However, its functional role in proliferation and progression of cancer cells remains unknown. The focus of this study was to investigate the molecular-mechanisms in which ERMP1 modulates the proliferation and progression of colorectal cancer (CRC) cells under normal and environment stress conditions.In this experimental study, ERMP1 expression was evaluated using reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) in CRC cells. ERMP1 was knocked down using lentiviral transduction of ERMP1-specific shRNA into HCT116 cells. ERMP1 was also upregulated using lipofectamine transfection of ERMP1-overexpressing vector into SW48 cells. To evaluate the role of ERMP1 in the cellular and environmental stress conditions, ERMP1-downregulated cells were exposed to stressful conditions including starvation, serum free medium, and treatment with redox or chemotherapy agents for 72 hours. The expression of AKT, p-AKT, phospho-mammalian target of rapamycin (p-mTOR), β-catenin, p-β-catenin, E-cadherin, and Glucose-regulating protein 78 (GRP78) proteins was evaluated by western blotting. The expression of ERMP1, CYCLIN D, and c-MYC was evaluated by RT-qPCR. The cell surface localization of GRP78, cell cycle distribution, and apoptosis were determined by Flow cytometry.ERMP1 knock-down reduced the cellular proliferation, inactivated the PI3K/AKT pathway, prompted the G1 arrest, and attenuated the free β-catenin and CYCLIN D expression. Opposite results were obtained in ERMP1- overexpressed cells. Knock-down of ERMP1 also reduced the GRP78 localization at the cell surface. Various environmental stress conditions differently affected the ERMP1-downregulated cells.ERMP1 functioned as an oncogene in CRC cells by promoting malignant characteristics. The phosphoinositide 3-kinases (PI3K)/AKT/β-catenin pathway and localization of GRP78 were closely related to the effects of ERMP1. Consequently, ERMP1 might be regarded as a promising target in therapeutic strategies related to CRC.