Background: Aspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growth in vivo. However, the impact of aspartate synthesis on metastasis has not been studied. We previously described that loss-of-aspartate glutamate carrier 1 (SLC25A12 or AGC1), an important component of the malate-aspartate shuttle, impairs cytosolic aspartate levels, NAD+/NADH ratio, mitochondrial respiration, and tumor growth. Here, we report the impact of AGC1-knockdown on metastasis. Results: AGC1 expression is positively correlated with worse patient prognosis in many cancers. AGC1-knockdown in mouse lung carcinoma and melanoma cell lines leads to increased pulmonary metastasis following subcutaneous or intravenous injections, respectively. On the other hand, conventional in vitro metastasis assays show no indication of increased metastasis capacity of AGC1-knockdown cells. Conclusion: This study highlights that certain branches of metabolism impact tumor growth and tumor metastasis differently. In addition, it also argues that commonly known metastasis indicators, including EMT genes, cell migration, or colony formation do not always reflect the metastatic capacity in vivo.

中文翻译：

---

苹果酸-天冬氨酸穿梭组分SLC25A12的丢失诱导肺转移

背景：天冬氨酸的生物合成及其向细胞质中的传递对于体内肿瘤的生长至关重要。但是，尚未研究天冬氨酸合成对转移的影响。我们先前曾描述过，谷氨酸-天门冬氨酸穿梭的重要组成部分-天冬氨酸谷氨酸载体1（SLC25A12或AGC1）受损，会损害胞液中的天冬氨酸水平，NAD + / NADH比，线粒体呼吸作用以及肿瘤的生长。在这里，我们报告AGC1组合式对转移的影响。结果：在许多癌症中，AGC1表达与患者预后较差呈正相关。皮下或静脉内注射后，小鼠肺癌和黑色素瘤细胞系中的AGC1敲低分别导致肺转移增加。另一方面，传统的体外转移试验未显示AGC1敲低细胞转移能力增强的迹象。结论：本研究强调某些代谢分支对肿瘤生长和肿瘤转移的影响不同。此外，它还认为，包括EMT基因，细胞迁移或集落形成在内的常见转移指标并不总是反映体内转移能力。