Targeting cancer metabolism at the plasma membrane by limiting amino acid access through SLC6A14.
Targeting cancer metabolism at the plasma membrane by limiting amino acid access through SLC6A14.
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DOI：
10.1042/bj20150721
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Edinger AL
中科院分区：
文献类型：
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作者：
McCracken AN;Edinger AL
正如 Babu 等人所描述的，癌症特异性营养转运蛋白 SLC6A14 可能是一种靶向癌症代谢的方法。在这个问题上。快速增殖的癌细胞通过合成代谢途径增加通量，以形成支持细胞分裂所需的质量。进口氨基酸和葡萄糖位于合成代谢金字塔的顶端。与此一致，营养转运蛋白表达升高是侵袭性和高度恶性癌症的特征。由于肿瘤细胞比正常细胞更依赖加速营养物质输入，因此这些上调的转运蛋白可能成为选择性抗癌疗法的绝佳靶标。巴布等人的一项研究。最近一期《生化杂志》明确表明，SLC6A14（其中 SLC 是溶质载体）是一种此类癌症特异性氨基酸转运蛋白。尽管完全缺乏 SLC6A14 的小鼠能够存活并表现出正常的乳腺发育，但这些动物对强癌基因驱动的乳腺肿瘤的发生和进展具有高度抵抗力。由于 SLC6A14 对于肿瘤生长至关重要，但对于正常发育和组织维护却是可有可无的，因此阻止氨基酸通过该转运蛋白输入的小分子可能是有效且选择性的抗癌药物，特别是作为合理药物组合的成分。
The cancer-specific nutrient transporter, SLC6A14, could be a means to target cancer metabolism as described by Babu et al. in this issue. Rapidly proliferating cancer cells increase flux through anabolic pathways to build the mass necessary to support cell division. Imported amino acids and glucose lie at the apex of the anabolic pyramid. Consistent with this, elevated expression of nutrient transporter proteins is characteristic of aggressive and highly malignant cancers. Because tumour cells are more dependent than their normal neighbours on accelerated nutrient import, these up-regulated transporters could be excellent targets for selective anti-cancer therapies. A study by Babu et al. in a recent issue of the Biochemical Journal definitively shows that SLC6A14 (where SLC is solute carrier) is one such cancer-specific amino acid transporter. Although mice completely lacking SLC6A14 are viable and exhibit normal mammary gland development, these animals are highly resistant to mammary tumour initiation and progression driven by potent oncogenes. Because SLC6A14 is essential for tumour growth yet dispensable for normal development and tissue maintenance, small molecules that block amino acid import through this transporter could be effective and selective anti-cancer agents, particularly as components of rational drug combinations.