Background Aspartate biosynthesis and its delivery to the cytosol can be crucial for tumor growth in vivo . However, the impact of intracellular aspartate levels 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 Low AGC1 expression correlates 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 metastatic capacity in vivo.

中文翻译：

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苹果酸-天冬氨酸穿梭组分 SLC25A12 的缺乏诱导肺转移

背景 天冬氨酸生物合成及其向胞质溶胶的递送对于体内肿瘤生长至关重要。然而，尚未研究细胞内天冬氨酸水平对转移的影响。我们之前描述了天冬氨酸谷氨酸载体 1（SLC25A12 或 AGC1）的缺失（苹果酸-天冬氨酸穿梭的重要组成部分）会损害胞质天冬氨酸水平、NAD + /NADH 比率、线粒体呼吸和肿瘤生长。在这里，我们报告了 AGC1 敲低对转移的影响。结果 在许多癌症中，低 AGC1 表达与较差的患者预后相关。小鼠肺癌和黑色素瘤细胞系中的 AGC1 敲低分别导致皮下或静脉注射后肺转移增加。另一方面，常规的体外转移测定没有显示 AGC1 敲低细胞的转移能力增加的迹象。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，众所周知的转移指标，包括 EMT 基因、细胞迁移或集落形成，并不总是反映体内转移能力。