丝氨酸合成增加促进丝氨酸水平受限的组织中出现肿瘤，这一成果由科赫癌症综合研究所Matthew G. Vander Heiden课题组取得。 相关论文于2019年3月21日发表在《Cell Metabolism》上。

研究团队证明，在黑色素瘤和乳腺癌的小鼠模型中， PHGDH表达的增加促进了肿瘤的进展，在人类肿瘤中PHGDH的拷贝数增加。课题组测量了循环丝氨酸水平，发现PHGDH的表达对于在较低的生理丝氨酸浓度下支持细胞增殖是必要的。增加膳食丝氨酸或高PHGDH表达足以增加细胞内丝氨酸水平并支持更快的肿瘤生长。数据表明，生理丝氨酸可用性抑制肿瘤生长，并在丝氨酸限制的环境中产生的肿瘤通过上调丝氨酸合成途径酶获得了适应性优势。

研究人员表示，与正常组织相比，肿瘤的代谢发生了改变。许多肿瘤上调丝氨酸合成途径酶的表达，一些肿瘤表现出编码该途径第一种酶的基因的拷贝数增加，即磷酸甘油脱氢酶(PHGDH)。然而，增加的丝氨酸合成是否促进肿瘤生长和丝氨酸合成如何有利于肿瘤是有争议的。

附：英文原文


Title: Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting

Author: Mark R. Sullivan, Katherine R. Mattaini, Emily A. Dennstedt, Marcus W. Bosenberg, Caroline A. Lewis, Matthew G. Vander Heiden

Issue&Volume: Jun 04, 2019 Volume 29Issue 6

Abstract: Tumors exhibit altered metabolism compared to normal tissues. Many cancers upregulate expression of serine synthesis pathway enzymes, and some tumors exhibit copy-number gain of the gene encoding the first enzyme in the pathway, phosphoglycerate dehydrogenase ( PHGDH). However, whether increased serine synthesis promotes tumor growth and how serine synthesis benefits tumors is controversial. Here, we demonstrate that increased PHGDH expression promotes tumor progression in mouse models of melanoma and breast cancer, human tumor types that exhibit PHGDH copy-number gain. We measure circulating serine levels and find that PHGDH expression is necessary to support cell proliferation at lower physiological serine concentrations. Increased dietary serine or high PHGDH expression is sufficient to increase intracellular serine levels and support faster tumor growth. Together, these data suggest that physiological serine availability restrains tumor growth and argue that tumors arising in serine-limited environments acquire a fitness advantage by upregulating serine synthesis pathway enzymes.

DOI: https://doi.org/10.1016/j.cmet.2019.02.015

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30125-1