Dysregulated metabolism is a hallmark of cancer that supports tumor growth and metastasis. One understudied aspect of cancer metabolism is altered nucleotide sugar biosynthesis, which drives aberrant cell surface glycosylation known to support various aspects of cancer cell behavior including migration and signaling. We examined clinical association of nucleotide sugar pathway gene expression and found that UGDH, encoding UDP-glucose 6-dehydrogenase which catalyzes production of UDP-glucuronate, is associated with worse breast cancer patient survival. Knocking out the mouse homolog Ugdh in highly-metastatic 6DT1 breast cancer cells impaired migration ability without affecting in vitro proliferation. Further, Ugdh-KO resulted in significantly decreased metastatic capacity in vivo when the cells were orthotopically injected in syngeneic mice. Our experiments show that UDP-glucuronate biosynthesis is critical for metastasis in a mouse model of breast cancer.

中文翻译：

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UDP葡萄糖6-脱氢酶的基因敲除会损害乳腺癌细胞的迁移并降低其体内转移能力。

代谢失调是支持肿瘤生长和转移的癌症的标志。癌症代谢的一个尚未被研究的方面是核苷酸糖生物合成的改变，其驱动异常的细胞表面糖基化，已知其支持癌细胞行为的各个方面，包括迁移和信号传导。我们检查了核苷酸糖途径基因表达的临床关联，发现编码UDP-葡萄糖6-脱氢酶的UDP编码UDP-葡萄糖醛酸的生产的UGDH与较差的乳腺癌患者生存率有关。在高度转移的6DT1乳腺癌细胞中剔除小鼠同源物Ugdh会损害迁移能力，而不会影响体外增殖。此外，当在同系小鼠中原位注射细胞时，Ugdh-KO导致体内转移能力显着降低。