Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis.

ABSTRACT:

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, conve

SUBMITTER: Alkan HF 

PROVIDER: S-EPMC7690131 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature