Liu Na, Zhu Xiao-Ren, Wu Chang-Ying, Liu Yuan-Yuan, Chen Min-Bin, Gu Jin-Hua
Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
Department of Intensive Care Medicine, Chongqing People's Hospital, Chongqing, China.
Cell Death Discov. 2024 Nov 22;10(1):478. doi: 10.1038/s41420-024-02240-8.
Recently, changes in metabolites and metabolism-related enzymes related to tumor cell proliferation, metastasis, drug resistance, and immunosuppression have become a research hotspot, and researchers have attempted to determine the clinical correlation between specific molecular lesions and metabolic phenotypes. Convincing evidence shows that metabolic reprogramming is closely related to the proliferation, invasion, metastasis, and poor prognosis of malignant tumors. Therefore, targeting metabolic reprogramming is a new direction for cancer treatment. However, how molecular alterations in tumors contribute to metabolic diversity and unique targeting dependencies remains unclear. A full understanding of the underlying mechanisms of metabolic reprogramming in cancer may lead to better identification of therapeutic targets and the development of therapeutic strategies. Evidence for the importance of PCK1, a phosphoenolpyruvate carboxykinase 1, in tumorigenesis and development is accumulating. PCK1 can regulate cell proliferation and metastasis by remodeling cell metabolism. Additionally, PCK1 has "nonclassical" nonmetabolic functions, involving the regulation of gene expression, angiogenesis, epigenetic modification, and other processes, and has an impact on cell survival, apoptosis, and other biological activities, as well as the remodeling of the tumor immune microenvironment. Herein, we provide a comprehensive overview of the functions of PCK1 under physiological and pathological conditions and suggest that PCK1 is a potential target for cancer therapy. We also propose a future exploration direction for targeting PCK1 for cancer therapy from a clinical perspective. Finally, in view of the collective data, the results of our discussion suggest the potential clinical application of targeted PCK1 therapy in combination with chemotherapy and immunotherapy for cancer treatment.
近年来，与肿瘤细胞增殖、转移、耐药及免疫抑制相关的代谢物和代谢相关酶的变化已成为研究热点，研究人员试图确定特定分子病变与代谢表型之间的临床关联。有说服力的证据表明，代谢重编程与恶性肿瘤的增殖、侵袭、转移及不良预后密切相关。因此，靶向代谢重编程是癌症治疗的一个新方向。然而，肿瘤中的分子改变如何导致代谢多样性和独特的靶向依赖性仍不清楚。全面了解癌症中代谢重编程的潜在机制可能有助于更好地识别治疗靶点并制定治疗策略。磷酸烯醇式丙酮酸羧激酶1（PCK1）在肿瘤发生发展中的重要性证据正在不断积累。PCK1可通过重塑细胞代谢来调节细胞增殖和转移。此外，PCK1具有“非经典”的非代谢功能，涉及基因表达调控、血管生成、表观遗传修饰等过程，并对细胞存活、凋亡等生物学活性以及肿瘤免疫微环境的重塑产生影响。在此，我们全面概述了PCK1在生理和病理条件下的功能，并表明PCK1是癌症治疗的潜在靶点。我们还从临床角度提出了靶向PCK1进行癌症治疗的未来探索方向。最后，鉴于汇总数据，我们的讨论结果表明靶向PCK1治疗联合化疗和免疫疗法在癌症治疗中的潜在临床应用。
