TBK1 Reprograms Metabolism in Breast Cancer: An Integrated Omics Approach

Area of Science:

• Oncology
• Molecular Biology
• Cancer Metabolism

Background:

• Metabolic rewiring is a hallmark of cancer, enabling survival and metastasis.
• TBK1 (TANK-binding kinase 1) is overexpressed in cancers and linked to poor prognosis, but its role in tumor metabolism is unclear.

Purpose of the Study:

• To investigate the novel role of TBK1 in regulating cancer cell metabolism.
• To elucidate the molecular mechanisms underlying TBK1's oncogenic function in metabolic adaptation.

Main Methods:

• Utilized combined metabolomics, transcriptomics, and pharmacological approaches.
• Investigated the impact of TBK1 on specific metabolic pathways and gene regulation.

Main Results:

• TBK1 regulates nucleotide and energy metabolism by controlling aldo-keto reductase B10 (AKRB10) and thymidine phosphorylase (TYMP) gene expression.
• TBK1-mediated metabolic rewiring contributes to its oncogenic function.
• TBK1 inhibitors show synergistic effects with AKRB10 and TYMP inhibitors in reducing cancer cell viability.

Conclusions:

• TBK1 plays a significant role in cancer cell metabolic adaptation.
• Targeting TBK1, AKRB10, and TYMP concurrently presents a potential therapeutic strategy for cancers with high TBK1 levels.