Program in Cancer Biology, Vanderbilt University, Nashville, TN, 37232, USA.
Department of Medicine, Division of Rheumatology, Vanderbilt University Medical Center, Nashville, TN, USA.
Oncogene. 2023 Nov;42(47):3447-3456. doi: 10.1038/s41388-023-02868-3. Epub 2023 Oct 18.
Most cancer-related deaths are caused by the metastases, which commonly develop at multiple organ sites including the brain, bone, and lungs. Despite longstanding observations that the spread of cancer is not random, our understanding of the mechanisms that underlie metastatic spread to specific organs remains limited. However, metabolism has recently emerged as an important contributor to metastasis. Amino acids are a significant nutrient source to cancer cells and their metabolism which can serve to fuel biosynthetic pathways capable of facilitating cell survival and tumor expansion while also defending against oxidative stress. Compared to the primary tumor, each of the common metastatic sites exhibit vastly different nutrient compositions and environmental stressors, necessitating the need of cancer cells to metabolically thrive in their new environment during colonization and outgrowth. This review seeks to summarize the current literature on amino acid metabolism pathways that support metastasis to common secondary sites, including impacts on immune responses. Understanding the role of amino acids in secondary organ sites may offer opportunities for therapeutic inhibition of cancer metastasis.
大多数与癌症相关的死亡都是由转移引起的，转移通常发生在多个器官部位，包括大脑、骨骼和肺部。尽管长期以来人们观察到癌症的扩散并非随机，但我们对导致特定器官转移的机制的理解仍然有限。然而，代谢最近已成为转移的一个重要贡献者。氨基酸是癌细胞的重要营养来源，其代谢可以为生物合成途径提供燃料，这些途径能够促进细胞存活和肿瘤扩张，同时抵御氧化应激。与原发性肿瘤相比，常见的转移部位中的每一个都表现出截然不同的营养成分和环境胁迫，这使得癌细胞在定植和生长过程中需要在新环境中进行代谢以茁壮成长。本综述旨在总结支持常见继发性部位转移的氨基酸代谢途径的现有文献，包括对免疫反应的影响。了解氨基酸在次级器官部位的作用可能为抑制癌症转移的治疗提供机会。
