Wang Hao, Yi Zhongquan, Yan Song, Wang Yihao, Zhang Weisong, Guo Rongqi, Li Yangyang, Wang Rui, Li Heng, Li Xia, Song JianXiang
Department of Cardiothoracic Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, Yancheng, 224000, People's Republic of China.
Department of Central Laboratory, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, Yancheng, 224000, People's Republic of China.
Onco Targets Ther. 2025 Jul 28;18:821-832. doi: 10.2147/OTT.S537194. eCollection 2025.
ORMDL proteins (ORMDL1, ORMDL2, ORMDL3) are transmembrane proteins in the endoplasmic reticulum (ER) that regulate sphingolipid metabolism, maintain ER homeostasis, and modulate cellular stress responses. They influence cell proliferation, apoptosis, and metabolic balance. Recent studies have highlighted the altered expression and function of ORMDL proteins in various tumors, including breast cancer, DLBCL, colorectal cancer, and lung cancer. ORMDLs negatively regulate serine palmitoyltransferase (SPT), affecting ceramide and sphingolipid metabolism, which plays a key role in tumor cell proliferation, invasiveness, and resistance to therapy. The dysregulation of ORMDL expression may disrupt sphingolipid metabolism, trigger ER stress, and impair autophagy. Investigating ORMDL functions in cancer could lead to novel insights into tumor development and progression. ORMDL expression may serve as a potential biomarker for cancer diagnosis, prognosis, and therapeutic response prediction. Targeting ORMDL or its metabolic networks offers promising strategies for cancer therapy. Although research on ORMDLs is still in its early stages, further studies are needed to explore their roles in the tumor microenvironment, interactions with the immune system, and applications in personalized medicine. A deeper understanding of ORMDL proteins will enhance tumor diagnosis, treatment, and the development of new therapeutic approaches.
ORMDL蛋白（ORMDL1、ORMDL2、ORMDL3）是内质网（ER）中的跨膜蛋白，可调节鞘脂代谢、维持内质网稳态并调节细胞应激反应。它们影响细胞增殖、凋亡和代谢平衡。最近的研究强调了ORMDL蛋白在包括乳腺癌、弥漫性大B细胞淋巴瘤（DLBCL）、结直肠癌和肺癌在内的各种肿瘤中的表达和功能改变。ORMDL蛋白负向调节丝氨酸棕榈酰转移酶（SPT），影响神经酰胺和鞘脂代谢，这在肿瘤细胞增殖、侵袭性和对治疗的抗性中起关键作用。ORMDL表达失调可能会破坏鞘脂代谢、引发内质网应激并损害自噬。研究ORMDL蛋白在癌症中的功能可能会为肿瘤发展和进展带来新的见解。ORMDL表达可能作为癌症诊断、预后和治疗反应预测的潜在生物标志物。靶向ORMDL或其代谢网络为癌症治疗提供了有前景的策略。尽管对ORMDL蛋白的研究仍处于早期阶段，但仍需要进一步研究以探索它们在肿瘤微环境中的作用、与免疫系统的相互作用以及在个性化医学中的应用。对ORMDL蛋白的更深入理解将提高肿瘤诊断、治疗以及新治疗方法的开发。
