Cui Hongwei, Jiang Li, Zhou Yujiao, Zhou You, Li Fan, Zhang Zhenzhen
The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Department of Infectious Disease, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, No.20 Jinyu Road, Yubei District, Chongqing, 401122, China.
Funct Integr Genomics. 2024 Dec 4;24(6):225. doi: 10.1007/s10142-024-01497-7.
Metastasis is responsible for approximately 90% of lethality from solid tumors. Metabolic abnormalities are one of the key characteristics of tumor cells, closely associated with tumorigenesis and progression. The de novo synthesis pathway of serine is a key metabolic bypass in glycolysis, which could provide material and energy basis for the rapid proliferation of tumor cells by mediating one-carbon metabolism. The transformation of metabolic patterns is particularly pronounced in HCC, often leading to a high dependence of HCC cells on glycolysis. However, up to now, the underlying relationship between serine metabolism and HCC metastasis remains largely unknown. Through a series of bioinformatics methods, we reported CCT6A, a serine related gene, was particularly associated with metastatic events of HCC. We furtherly demonstrated that CCT6A was highly expressed in HCC cells with high metastatic potential. Gain- and loss-of-function analyses showed that CCT6A could promote HCC cells migration and invasion. Mechanistically, CCT6A was found to be interacted with RPS3, and might potentiate the metastasis of HCC by affecting some metabolic processes. Totally, our results suggest that the metabolic reprogramming induced by interacting between CCT6A and RPS3 could advance HCC metastasis, making the CCT6A/RPS3 axis a promising target for therapeutic intervention.
转移是实体瘤致死率约90%的原因。代谢异常是肿瘤细胞的关键特征之一,与肿瘤发生和进展密切相关。丝氨酸的从头合成途径是糖酵解中的关键代谢旁路,可通过介导一碳代谢为肿瘤细胞的快速增殖提供物质和能量基础。代谢模式的转变在肝癌中尤为明显,常导致肝癌细胞对糖酵解的高度依赖。然而,迄今为止,丝氨酸代谢与肝癌转移之间的潜在关系仍 largely未知。通过一系列生物信息学方法,我们报道了丝氨酸相关基因CCT6A与肝癌转移事件特别相关。我们进一步证明CCT6A在具有高转移潜能的肝癌细胞中高表达。功能获得和缺失分析表明CCT6A可促进肝癌细胞迁移和侵袭。机制上,发现CCT6A与RPS3相互作用,并可能通过影响一些代谢过程增强肝癌转移。总之,我们的结果表明CCT6A与RPS3相互作用诱导的代谢重编程可促进肝癌转移,使CCT6A/RPS3轴成为治疗干预的有希望靶点。