bims-mecami 2024-07-28 papers

Issue of 2024–07–28
four papers selected by
Oltea Sampetrean, Keio University

Cell. 2024 Jul 25. pii: S0092-8674(24)00700-1. [Epub ahead of print]187(15): 3824-3828

100 years of the Warburg effect: A cancer metabolism endeavor.

If you are a scientist and you only know one thing about tumor metabolism, it's likely the Warburg effect. But who was Otto Warburg, and how did his discoveries regarding the metabolism of tumors shape our current thinking about the metabolic needs of cancer cells?

DOI: https://doi.org/10.1016/j.cell.2024.06.026

Ann Oncol. 2024 Jul 23. pii: S0923-7534(24)01495-9. [Epub ahead of print]

Exploiting the tumor microenvironment and tumor mechanobiology for the treatment of cancer cachexia.

Kostas A Papavassiliou, Athanasios G Papavassiliou.

Keywords: Cancer cachexia; Fibrosis; Inhibitors; Mechanosignaling; Targeting; Tumor microenvironment

DOI: https://doi.org/10.1016/j.annonc.2024.07.721

Metabolites. 2024 Jul 11. pii: 383. [Epub ahead of print]14(7):

Challenges of Spatially Resolved Metabolism in Cancer Research.

Andrew N Lane, Richard M Higashi, Teresa W-M Fan.

Stable isotope-resolved metabolomics comprises a critical set of technologies that can be applied to a wide variety of systems, from isolated cells to whole organisms, to define metabolic pathway usage and responses to perturbations such as drugs or mutations, as well as providing the basis for flux analysis. As the diversity of stable isotope-enriched compounds is very high, and with newer approaches to multiplexing, the coverage of metabolism is now very extensive. However, as the complexity of the model increases, including more kinds of interacting cell types and interorgan communication, the analytical complexity also increases. Further, as studies move further into spatially resolved biology, new technical problems have to be overcome owing to the small number of analytes present in the confines of a single cell or cell compartment. Here, we review the overall goals and solutions made possible by stable isotope tracing and their applications to models of increasing complexity. Finally, we discuss progress and outstanding difficulties in high-resolution spatially resolved tracer-based metabolic studies.

Keywords: cancer metabolism; experimental models; spatially resolved metabolism; stable isotope-resolved metabolomics

DOI: https://doi.org/10.3390/metabo14070383

Redox Biol. 2024 Jul 20. pii: S2213-2317(24)00254-4. [Epub ahead of print]75 103276

Metastatic breast cancer cells are metabolically reprogrammed to maintain redox homeostasis during metastasis.

Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. We have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic program characterized by increased HIF-1α activity and dependence on glycolysis. Here, we confirm by in vivo stable isotope tracing analysis (SITA) that liver-metastatic breast cancer cells retain a glycolytic profile when grown as mammary tumors or liver metastases. However, hepatic metastases exhibit unique metabolic adaptations including elevated expression of genes involved in glutathione (GSH) biosynthesis and reactive oxygen species (ROS) detoxification when compared to mammary tumors. Accordingly, breast-cancer-liver-metastases exhibited enhanced de novo GSH synthesis. Confirming their increased capacity to mitigate ROS-mediated damage, liver metastases display reduced levels of 8-Oxo-2'-deoxyguanosine. Depletion of the catalytic subunit of the rate-limiting enzyme in glutathione biosynthesis, glutamate-cysteine ligase (GCLC), strongly reduced the capacity of breast cancer cells to form liver metastases, supporting the importance of these distinct metabolic adaptations. Loss of GCLC also affected the early steps of the metastatic cascade, leading to decreased numbers of circulating tumor cells (CTCs) and impaired metastasis to the liver and the lungs. Altogether, our results indicate that GSH metabolism could be targeted to prevent the dissemination of breast cancer cells.

Keywords: Breast cancer; GCLC; Glutathione; Glycolysis; HIF-1α; Liver metastasis; Metabolism; Oxidative stress

DOI: https://doi.org/10.1016/j.redox.2024.103276