Departments of Biomedical Sciences and Clinical & Translational Science, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV 25755, USA.
Int J Mol Sci. 2018 Aug 12;19(8):2373. doi: 10.3390/ijms19082373.
The progression of cancer is associated with increases in amino acid uptake by cancer cells. Upon their entry into cells through specific transporters, exogenous amino acids are used to synthesize proteins, nucleic acids and lipids and to generate ATP. The essential amino acid leucine is also important for maintaining cancer-associated signaling pathways. By upregulating amino acid transporters, cancer cells gain greater access to exogenous amino acids to support chronic proliferation, maintain metabolic pathways, and to enhance certain signal transduction pathways. Suppressing cancer growth by targeting amino acid transporters will require an in-depth understanding of how cancer cells acquire amino acids, in particular, the transporters involved and which cancer pathways are most sensitive to amino acid deprivation. L-Type Amino Acid Transporter 1 (LAT1) mediates the uptake of essential amino acids and its expression is upregulated during the progression of several cancers. We will review the upstream regulators of LAT1 and the downstream effects caused by the overexpression of LAT1 in cancer cells.
癌症的发展与癌细胞对氨基酸的摄取增加有关。氨基酸通过特定的转运蛋白进入细胞后，被用于合成蛋白质、核酸和脂质，并产生 ATP。必需氨基酸亮氨酸对于维持与癌症相关的信号通路也很重要。通过上调氨基酸转运蛋白，癌细胞可以更有效地获取外源性氨基酸，以支持其慢性增殖、维持代谢途径，并增强某些信号转导途径。通过靶向氨基酸转运蛋白来抑制癌症生长，需要深入了解癌细胞获取氨基酸的方式，特别是涉及的转运蛋白以及哪些癌症途径对氨基酸缺乏最敏感。L 型氨基酸转运蛋白 1（LAT1）介导必需氨基酸的摄取，其表达在几种癌症的进展过程中上调。我们将回顾 LAT1 的上游调节剂以及 LAT1 在癌细胞中过表达所引起的下游效应。
