Abstract：
The non-essential amino acid serine is a critical nutrient for cancer cells due to its diverse biosynthetic functions. While some tumors can synthesize serine de novo, others are auxotrophic and therefore reliant on serine uptake. Importantly, despite several transporters being known to be capable of transporting serine, the transporters that mediate serine uptake in cancer cells are not known. Here, we characterize the amino acid transporter ASCT2 (SLC1A5) as a major contributor to serine uptake in cancer cells. ASCT2 is well known as a glutamine transporter in cancer, and our work demonstrates that serine and glutamine compete for uptake through ASCT2. We further show that ASCT2-mediated serine uptake is essential for purine nucleotide biosynthesis and that estrogen receptor α (ERα) promotes serine uptake by directly activating SLC1A5 transcription. Collectively, our work defines an additional important role for ASCT2 as a serine transporter in cancer and evaluates ASCT2 as a potential therapeutic target.
摘要：
非必需氨基酸丝氨酸由于其多种生物合成功能而成为癌细胞的关键营养素。虽然一些肿瘤可以从头合成丝氨酸，其他是营养缺陷型，因此依赖于丝氨酸的摄取。重要的是,尽管已知有几种转运蛋白能够转运丝氨酸，在癌细胞中介导丝氨酸摄取的转运蛋白是未知的。这里,我们将氨基酸转运蛋白ASCT2（SLC1A5）描述为癌细胞中丝氨酸摄取的主要贡献者。ASCT2是众所周知的癌症中的谷氨酰胺转运蛋白，我们的工作表明丝氨酸和谷氨酰胺竞争通过ASCT2摄取。我们进一步表明，ASCT2介导的丝氨酸摄取对于嘌呤核苷酸生物合成至关重要，并且雌激素受体α（ERα）通过直接激活SLC1A5转录来促进丝氨酸摄取。总的来说，我们的工作确定了ASCT2作为丝氨酸转运蛋白在癌症中的另一个重要作用,并评估了ASCT2作为潜在治疗靶点的作用.
