4.8 Article

Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2205456119

Keywords

triple negative breast cancer; metastasis j gene expression; genome-scale metabolic models; systems biology

Funding

  1. University of Tehran, Iran
  2. Knut and Alice Wallenberg foundation

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This study utilized transcriptomic data and metabolic network analyses to investigate the adaptation of metastatic tumors to the local metabolic environment. The findings suggest that metastatic tumors adopt a metabolic signature similar to their destination's primary tumors, but the extent of adaptation varies across different organs. Metastatic tumors also retain metabolic signatures associated with TNBC.
Triple negative breast cancer (TNBC) metastases are assumed to exhibit similar functions in different organs as in the original primary tumor. However, studies of metastasis are often limited to a comparison of metastatic tumors with primary tumors of their origin, and little is known about the adaptation to the local environment of the metastatic sites. We therefore used transcriptomic data and metabolic network analyses to investigate whether metastatic tumors adapt their metabolism to the metastatic site and found that metastatic tumors adopt a metabolic signature with some similarity to primary tumors of their destinations. The extent of adaptation, however, varies across different organs, and metastatic tumors retain metabolic signatures associated with TNBC. Our findings suggest that a combination of anti-metastatic approaches and metabolic inhibitors selected specifically for different metastatic sites, rather than solely targeting TNBC primary tumors, may constitute a more effective treatment approach.

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