Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, No. 467 Zhongshan Road, Dalian, 116023, China.
Cancer Translational Medicine Research Center, The Second Hospital, Dalian Medical University, Dalian, 116023, China.
J Transl Med. 2021 Mar 21;19(1):118. doi: 10.1186/s12967-021-02786-6.
Glucose-regulating protein 78 (GRP78) is a molecular chaperone in the endoplasmic reticulum (ER) that promotes folding and assembly of proteins, controls the quality of proteins, and regulates ER stress signaling through Ca binding to the ER. In tumors, GRP78 is often upregulated, acting as a central stress sensor that senses and adapts to changes in the tumor microenvironment, mediating ER stress of cancer cells under various stimulations of the microenvironment to trigger the folding protein response. Increasing evidence has shown that GRP78 is closely associated with the progression and poor prognosis of lung cancer, and plays an important role in the treatment of lung cancer. Herein, we reviewed for the first time the functions and mechanisms of GRP78 in the pathological processes of lung cancer, including tumorigenesis, apoptosis, autophagy, progression, and drug resistance, giving a comprehensive understanding of the function of GRP78 in lung cancer. In addition, we also discussed the potential role of GRP78 as a prognostic biomarker and therapeutic target for lung cancer, which is conducive to improving the assessment of lung cancer and the development of new therapeutic interventions.
葡萄糖调节蛋白 78(GRP78)是内质网(ER)中的一种分子伴侣,可促进蛋白质的折叠和组装,控制蛋白质的质量,并通过与 ER 的 Ca 结合来调节 ER 应激信号。在肿瘤中,GRP78 通常上调,作为中央应激传感器,感知和适应肿瘤微环境的变化,介导癌细胞在微环境的各种刺激下的 ER 应激,从而触发折叠蛋白反应。越来越多的证据表明,GRP78 与肺癌的进展和不良预后密切相关,在肺癌的治疗中发挥着重要作用。在此,我们首次综述了 GRP78 在肺癌发生、凋亡、自噬、进展和耐药等病理过程中的作用及其机制,全面了解了 GRP78 在肺癌中的功能。此外,我们还讨论了 GRP78 作为肺癌预后生物标志物和治疗靶点的潜在作用,这有助于改善对肺癌的评估和新治疗干预措施的开发。