内质网应激及其在骨肉瘤中作用的研究进展

Research progress of endoplasmic reticulum stress and its role in osteosarcoma

骨肉瘤是最常见的恶性骨肿瘤,常发生在儿童和青少年中。近几十年来,针对骨肉瘤的治疗和干预措施也得到了不断地探索和研究,但是目前常规的放化疗和手术切除等治疗措施仍然存在很大程度上的不足^([1-2])。骨肉瘤是一种具有明显异质性的肿瘤,无论是在肿瘤细胞内还是细胞间质内,都未发现确定的肿瘤驱动因子。因此针对骨肉瘤细胞的分子靶向疗法的研究变得十分困难。目前的研究认为,肿瘤细胞的死亡途径主要有5种:细胞凋亡、细胞焦亡、坏死性凋亡、铁死亡、自噬。

Endoplasmic reticulum(ER)is a key organelle for cell function and metabolic adaptation.Disrupted ER homeostasis,including hypoxia,insufficient amino acid supply and lactic acidosis,will lead to ER stress(ERS),further unfolded protein response(UPR),ER associated protein degradation(ERAD),activation of autophagy pathway and other abnormal reactions,resulting in metabolic disorders of some important proteins in the body.It has been confrmed that ERS is involved in the pathogenesis of diabetes,breast cancer,lung cancer,prostate cancer and other diseases.Reganding the role of ERS in osteosarcoma,there are some latest research results at home and abroad.In this paper,we reviewed the mechanisms of endoplasmic reticulum stress and related signaling pathways targeting Ca2+,reactive oxygen species(ROS),epithelial mesenchymal transformation(EMT),ncRNA,etc.,in order to provide new ideas for future research and treatment strategies of osteosarcoma.