We found increased expression of HIF- 1α and HIF-1β mRNA, as well as the target genes, VEGF, and PFKFB3 in both MDD and BPD patients in a depressive state compared to healthy control subjects.
PFKFB3, a potential regulator of glycolysis, displays decreased mRNA levels in adipose tissue of obese women, is associated with obesity and is a new promising candidate gene for obesity warranting further studies.
We found increased expression of HIF- 1α and HIF-1β mRNA, as well as the target genes, VEGF, and PFKFB3 in both MDD and BPD patients in a depressive state compared to healthy control subjects.
Inhibition of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) diminishes cancer cell proliferation and tumour growth in animals.
Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling.
IDH-wildtype glioblastomas showed lower PFKFB3 to PFKFB4 mRNA ratios (7.7:1) than IDH-mutant low-grade astrocytomas (36.5:1), indicating a dependency of the ratio on malignancy grade.
The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG-1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.
In summary, we identify a key role for PFKFB3 enzymatic activity in HR repair and present KAN0438757, a selective PFKFB3 inhibitor that could potentially be used as a strategy for the treatment of cancer.
Expert opinion: PFKFB3 plays an important role in sustaining the development and progression of cancer and might represent an attractive target for therapeutic strategies.
This inducible gene for PFK-2 is expressed constitutively in several human cancer cell lines and was found to be required for tumor cell growth in vitro and in vivo.
Taken together, these findings demonstrate PFKFB3 as a mediator of circadian control of cancer growth, thereby highlighting the importance of time-based PFKFB3 inhibition in cancer treatment.
The expression of these mRNAs is increased in malignant tumors and strongly induced in different cancer cell lines by hypoxia inducible factor (HIF) through active HIF binding sites in promoter region of PFKFB-4 and PFKFB-3 genes.
This study provides a new insight into the roles of PFKFB3 as switch that senses and controls redox homeostasis in cancer in addition to its role in cancer glycolysis.
In this review, we summarize current knowledge of PFKFB3 regulation by several signal pathways and its function in cancer development in different cell types in cancer tissues.
The pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy.
The pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy.