MUC1 facilitates metabolomic reprogramming in triple-negative breast cancer.
MUC1 facilitates metabolomic reprogramming in triple-negative breast cancer.
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DOI：
10.1371/journal.pone.0176820
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Singh PK
中科院分区：
文献类型：
--
作者：
Goode G;Gunda V;Chaika NV;Purohit V;Yu F;Singh PK
Mucin1 （MUC1）是一种与化疗耐药和侵袭性癌症表型相关的糖蛋白，在三阴性乳腺癌（TNBC）中异常过表达。最近的研究表明，MUC1在调节癌细胞代谢中发挥作用，从而支持肿瘤生长。在此，我们研究了MUC1在TNBC代谢重编程中的作用。MUC1在MDA-MB-231 TNBC细胞中稳定过表达，在MDA-MB-468细胞中稳定低表达。我们进行了液相色谱-串联质谱辅助代谢组学分析和生理分析，结果表明由于MUC1的表达，TNBC细胞的代谢发生了显著变化。差异分析确定了与癌细胞生长有关的代谢途径的显著差异。特别是MUC1的表达改变了细胞对谷氨酰胺的依赖性，这可以部分归因于调节谷氨酰胺代谢的基因表达的变化，通过实时PCR分析可以观察到。此外，MUC1的表达改变了细胞对转氨酶抑制剂氨基乙酸酯（AOA）的敏感性，可能是通过改变谷氨酰胺代谢来实现的。综上所述，这些结果表明MUC1在TNBC中作为代谢调节因子，促进谷氨酰胺利用的代谢重编程，影响TNBC肿瘤生长。
Mucin1 (MUC1), a glycoprotein associated with chemoresistance and an aggressive cancer phenotype, is aberrantly overexpressed in triple-negative breast cancer (TNBC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism and thereby supports tumor growth. Herein, we examined the role of MUC1 in metabolic reprogramming in TNBC. MUC1 was stably overexpressed in MDA-MB-231 TNBC cells and stably knocked down in MDA-MB-468 cells. We performed liquid chromatography-coupled tandem mass spectrometry-assisted metabolomic analyses and physiological assays, which indicated significant alterations in the metabolism of TNBC cells due to MUC1 expression. Differential analyses identified significant differences in metabolic pathways implicated in cancer cell growth. In particular, MUC1 expression altered glutamine dependency of the cells, which can be attributed in part to the changes in the expression of genes that regulate glutamine metabolism, as observed by real-time PCR analysis. Furthermore, MUC1 expression altered the sensitivity of cells to transaminase inhibitor aminooxyacetate (AOA), potentially by altering glutamine metabolism. Collectively, these results suggest that MUC1 serves as a metabolic regulator in TNBC, facilitating the metabolic reprogramming of glutamine utilization that influences TNBC tumor growth.