Glutamine as a context-dependent regulator controlling metabolism and immunity in triple-negative breast cancer
Year: 2026
Type: article
Abstract: Triple-negative breast cancer (TNBC) exhibits early metastasis, a unique metabolic rigidity and poor clinical outcomes. A substantial, biomarker-definable subset of TNBC depends on glutamine metabolism, which can act as a nutrient source and a regulator of proliferation, redox homeostasis, epigenetic remodelling, and immune evasion. Glutamine metabolism in TNBC involves several interrelated processes, including transporter regulation, transcriptional control (FOXM1/FUS/SLC7A5 axis), and organelle-specific redox adaptation (ER-PPP/H6PD pathway). Various transporters mediate the uptake of glutamine into the cells. Once inside the cells, glutamine undergoes enzymatic conversion, driving essential metabolic pathways that support the tumor’s energy needs, maintain cellular redox balance, and drive epigenetic changes that promote cancer progression. Furthermore, the tumor microenvironment, including spatial immune-metabolic competition/heterogeneity, is significantly influenced by glutamine metabolism. The availability of glutamine can regulate the behavior of immune cells, including T cells and macrophages, potentially leading to immune suppression and contributing to therapeutic resistance. We concluded that glutamine metabolism is a key dependency in a substantial, biomarker-definable subset of TNBC. The therapeutic potential of glutamine metabolism not only offers a promising avenue for improving treatment outcomes but also presents a means to overcome current therapeutic limitations in TNBC.
Source: Cell Communication and Signaling
Institution: Magna Graecia University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,390
OpenAlex ID: W7202364060