Sun Kai, Zhi Yuan, Ren Wenhao, Li Shaoming, Zheng Jingjing, Gao Ling, Zhi Keqian
Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Huangdao Distract, Qingdao, 266003, Shandong, China.
School of Stomatology, Qingdao University, Qingdao, 266003, China.
Exp Hematol Oncol. 2024 Nov 1;13(1):107. doi: 10.1186/s40164-024-00569-5.
Developing resistance to cancer treatments is a major challenge, often leading to disease recurrence and metastasis. Understanding the underlying mechanisms of therapeutic resistance is critical for developing effective strategies. O-GlcNAcylation, a post-translational modification that adds GlcNAc from the donor UDP-GlcNAc to serine and threonine residues of proteins, plays a crucial role in regulating protein function and cellular signaling, which are frequently dysregulated in cancer. Similarly, ubiquitination, which involves the attachment of ubiquitin to to proteins, is crucial for protein degradation, cell cycle control, and DNA repair. The interplay between O-GlcNAcylation and ubiquitination is associated with cancer progression and resistance to treatment. This review discusses recent discoveries regarding the roles of O-GlcNAcylation and ubiquitination in cancer resistance, their interactions, and potential mechanisms. It also explores how targeting these pathways may provide new opportunities to overcome cancer treatment resistance in cancer, offering fresh insights and directions for research and therapeutic development.
对癌症治疗产生耐药性是一项重大挑战，常常导致疾病复发和转移。了解治疗耐药性的潜在机制对于制定有效策略至关重要。O-连接的N-乙酰葡糖胺化（O-GlcNAcylation）是一种翻译后修饰，它将供体UDP-N-乙酰葡糖胺（UDP-GlcNAc）中的GlcNAc添加到蛋白质的丝氨酸和苏氨酸残基上，在调节蛋白质功能和细胞信号传导中起着关键作用，而这些在癌症中常常失调。同样，泛素化涉及将泛素附着到蛋白质上，对蛋白质降解、细胞周期控制和DNA修复至关重要。O-GlcNAcylation和泛素化之间的相互作用与癌症进展和治疗耐药性相关。本综述讨论了关于O-GlcNAcylation和泛素化在癌症耐药性中的作用、它们的相互作用以及潜在机制的最新发现。它还探讨了靶向这些途径如何可能为克服癌症治疗耐药性提供新机会，为研究和治疗开发提供新的见解和方向。
