Dissemin is shutting down on January 1st, 2025

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MDPI, International Journal of Molecular Sciences, 8(24), p. 7450, 2023

DOI: 10.3390/ijms24087450

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Crosstalk between Metabolite Production and Signaling Activity in Breast Cancer

Journal article published in 2023 by Cankut Çubuk, Carlos Loucera ORCID, María Peña-Chilet ORCID, Joaquin Dopazo ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.