Metabolic rewiring is required for cancer cells to survive in harsh microenvironments and is considered to be a hallmark of cancer. Specific metabolic adaptations are required for a tumor to become invasive and metastatic. Cell division and metabolism are inherently interconnected, and several cell cycle modulators directly regulate metabolism. Here, we report that TBK1, which is a noncanonical IKK kinase with known roles in cell cycle regulation and TLR signaling, affects cellular metabolism in cancer cells. While TBK1 is reported to be overexpressed in several cancers and its enhanced protein level correlates with poor prognosis, the underlying molecular mechanism involved in the tumor-promoting role of TBK1 is not fully understood. In this study, we show a novel role of TBK1 in regulating cancer cell metabolism using combined metabolomics, transcriptomics, and pharmacological approaches. We find that TBK1 mediates the regulation of nucleotide and energy metabolism through aldo-keto reductase B10 (AKRB10) and thymidine phosphorylase (TYMP) genes, suggesting that this TBK1-mediated metabolic rewiring contributes to its oncogenic function. In addition, we find that TBK1 inhibitors can act synergistically with AKRB10 and TYMP inhibitors to reduce cell viability. These findings raise the possibility that combining these inhibitors might be beneficial in combating cancers that show elevated levels of TBK1.

Meenu Maan

Neha Jaiswal

Min Liu

Harold I. Saavedra

Srikumar P. Chellappan

Mainak Dutta

Journal of Proteome Research

《蛋白质组研究杂志》出版内容涵盖全球蛋白质分析和功能的各个方面，包括基因组学、时空蛋白质组学、代谢组学和代谢组学、临床和农业蛋白质组学的动态方面，以及包括生物信息学在内的方法学进展。主题和重点是通过不同类型的“组学”之间的协同作用，对生命科学采取多学科方法。

The Journal of Proteome Research covers various aspects of global protein analysis and functionality, including genomics, spatiotemporal proteomics, metabolomics, and dynamic studies in clinical and agricultural proteomics, as well as methodological advancements including bioinformatics. The journal focuses on a multidisciplinary approach to life sciences through the synergy of different types of 'omics'.

《Journal of Proteome Research》涵盖全球蛋白质分析和功能的各个方面，包括基因组学、时空蛋白质组学、代谢组学、临床和农业蛋白质组学的动态研究，以及生物信息学等方法学的进展。该期刊的主题和重点是通过不同类型的“组学”之间的协同作用，采用多学科的方法来研究生命科学。

Category	Quartile
生物学	2
生物学, 生化研究方法	2

TBK1 Reprograms Metabolism in Breast Cancer: An Integrated Omics Approach

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Journal Info

Category	Quartile
BIOCHEMICAL RESEARCH METHODS	1