GLS2 (Glutaminase 2)

This integrative analysis highlights evolutionary divergence and TME heterogeneity across TET subtypes and identifies immunometabolic biomarkers that may support prognostic assessment and future personalised treatment stratification in aggressive TETs.

Pharmacological disruption of this N-terminal interaction by streptonigrin, in combination with standard chemotherapy, extended overall survival in a xenograft model of ovarian cancer. This study identified TGase 2 as a pivotal regulator of EMT-driven metastasis and drug resistance.

Our study reveals a novel mechanism by which PIK3CG-KD regulates Gln metabolism and mitochondrial function via the S6K2/P53/GLS2 axis, providing a rationale for metabolic intervention and precision therapy in PIK3CG-deficient PDAC.

Subcutaneous xenograft mouse models further verified these findings and the regulatory role of TGM2 in cervical cancer radiosensitivity in vivo. Together, our results demonstrated that TGM2 regulates radiosensitivity by POGZ-mediated DNA DSBs repair, providing a novel strategy for increasing cervical cancer radiosensitivity.

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.

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.

Anti-TG2 siRNA silencing reduced cisplatin IC50 to base levels in both wild-type and cisplatin-surviving MCF-7 cells, supporting the notion that the modulation of TG2 expression could offer a significant benefit to cisplatin efficacy. Preventing excessive retinoic acid exposure may also be a mechanism for maximising cisplatin efficacy, considering TG2 modulation.

The over-expression of transglutaminase-2 is associated with invasive disease in bladder cancer. According to our results, transglutaminase-2 has the potential to be useful for predicting the invasion in bladder cancer and addressing treatment.

Mechanistically, the suppression of GLS2 interacted with Cu to downregulate lipoic acid synthase and dihydrolipoamide S-succinyltransferase, resulting in the reduction of the activity of α-ketoglutarate dehydrogenase complex and the obstruction of the tricarboxylic acid cycle, ultimately leading to the enhancement of RT sensitivity. These findings emphasize the significance of cuproptosis in ESCC radiotherapy and provide potential directions for therapeutic strategies.

The present study revealed a novel mechanism by which hypoxia upregulates PD-L1 expression and highlighted the involvement of GLS2 in non-canonical metabolic pathways involved in tumour immune evasion, with implications for PDAC treatment.

Treatment with GLS inhibitor CB-839 was also included to concomitantly inhibit endogenous GLS...These changes suggest that GLS2 may be a key regulator linking glutamine and glucose metabolism, also impacting nucleotides and epigenetics. Future research should ascertain the mechanisms involved and the generalizability of these findings in cancer or physiological conditions.

Tissue compartment and hormone receptor status differences in the effect of TGM2 expression on clinical outcomes of breast cancer may reflect the different functions of TGM2.