Crosstalk between Metabolite Production and Signaling Activity in Breast Cancer.

TitleCrosstalk between Metabolite Production and Signaling Activity in Breast Cancer.
Publication TypeJournal Article
Year of Publication2023
AuthorsCubuk, C, Loucera, C, Peña-Chilet, M, Dopazo, J
JournalInt J Mol Sci
Volume24
Issue8
Date Published2023 Apr 18
ISSN1422-0067
Abstract

The reprogramming of metabolism is a recognized cancer hallmark. It is well known that different signaling pathways regulate and orchestrate this reprogramming that contributes to cancer initiation and development. However, recent evidence is accumulating, suggesting that several metabolites could play a relevant role in regulating signaling pathways. To assess the potential role of metabolites in the regulation of signaling pathways, both metabolic and signaling pathway activities of Breast invasive Carcinoma (BRCA) have been modeled using mechanistic models. Gaussian Processes, powerful machine learning methods, were used in combination with SHapley Additive exPlanations (SHAP), a recent methodology that conveys causality, to obtain potential causal relationships between the production of metabolites and the regulation of signaling pathways. A total of 317 metabolites were found to have a strong impact on signaling circuits. The results presented here point to the existence of a complex crosstalk between signaling and metabolic pathways more complex than previously was thought.

DOI10.3390/ijms24087450
Alternate JournalInt J Mol Sci
PubMed ID37108611