GLS1 (Glutaminase)

FOXA2 accelerated BCa cell proliferation and metastasis by promoting GLS1-mediated glutamine metabolism, providing a novel therapy target for BCa.

CB-839 increased the potency of STM2457 only in the LCC9 and ZR-75-1-4-OHT endocrine-resistant cells. Our collective findings suggest that METTL3 inhibition leads to selective glycolytic and oxidative metabolic changes between these endocrine-sensitive and resistant BC cells that can be exploited for combinatorial therapy.

Our study provides initial insights into the oncogenic roles of GLS1 across different tumors. These findings suggest that GLS1 can serve as a potential biomarker for determining prognosis and designing therapeutic strategies for various tumor types.

Inhibiting GLS1 with CB-839 significantly impacted glutamine metabolism in HCC cells while showing limited activity on normal hepatocytes...Overexpressed GLS1 and loss of GLS2 within tumors convey an unfavorable prognosis in patients with HCC. Pharmacological inhibition of GLS1 in HCC cells successfully harnesses glutamine metabolism, representing an attractive target for novel therapeutic approaches.

The AID model is a promising biomarker for accurately determining survival and predicting the effectiveness of immunotherapy in STAD patients. GLS1 plays a crucial role in driving tumor proliferation and migration and may act as a potential tumor biomarker of STAD.

Further research is warranted to explore functional mechanisms and validate these markers in diverse populations. This study provides novel insights into the metabolic dynamics of breast cancer, offering a foundation for regionally tailored therapeutic strategies.

These findings indicate that glutamine metabolism is upregulated in canine large-cell AL and plays a crucial role in tumour cell growth and survival. Inhibiting glutaminase could serve as a promising therapeutic strategy for this disease.

Using pharmacological agents, including dabrafenib (BRAFi), pimasertib (MEKi), dasatinib (cKITi), and CB-839 (glutaminase inhibitor), we explored metabolic adaptations in melanoma cell lines harboring various mutations. This study underscores the metabolic alterations driving resistance to BRAFi in melanoma cells and highlights the therapeutic potential of targeting glutaminolysis with CB-839. The identification of metabolic signatures in patient samples provides valuable insights for personalized treatment strategies, aiming to overcome resistance mechanisms and improve patient outcomes in melanoma management.

Glutamate can promote macrophage polarization and the development of TNBC by upregulating IRE1α/XBP-1. Targeted inhibition of glutamate metabolism or IRE1α/XBP-1 pathway can effectively block the proliferation of TNBC tumor cells, providing a basis for the study of targeted drugs to treat TNBC.

Together, these results identify YY2/GAC as a negative regulator of glutamine catabolism in tumor cells and reveal a novel molecular mechanism underlying the tumor-suppressive effect of YY2. Moreover, these findings suggest that YY2 could serve as an antitumor therapeutic agent by targeting glutamine metabolism.

This study explores a novel metabolism-based therapeutic approach using a polyurea generation 4 dendrimer (PUREG4) surface functionalized with lactate (LA) (PUREG4-LA24), to take advantage of glucose-dependent monocarboxylate transporters (MCTs) overexpression, loaded with selenium-chrysin (SeChry) and temozolomide (TMZ) or complexed with anti-glutaminase (GLS1) siRNAs to abrogate glutamine dependence...It efficiently knocked down GLS1. Moreover, PUREG4-LA24 loaded with SeChry led to BBB disruption.

Our findings indicate that increased glutaminase expression is associated with an immune-suppressive tumor microenvironment, poor clinicopathologic features, and worse long-term outcomes in patients with endometrial cancer.