STAT3 mediated regulation of glucose metabolism in leukemia cells.

Cancer cells rewire metabolic pathways as they demand more ATP and building blocks for proliferation. Glucose is the most consumed nutrient by cancer cells and metabolized to lactate even in the presence of oxygen. This phenomenon is called 'aerobic glycolysis'. Also, glucose level is found lower in tumor environment. Leukemia is characterized by abnormal proliferation of hematopoietic cells. STAT3 a transcription factor and an oncogene is upregulated in many tumor types. Despite its well-defined functions, STAT3 has also been proposed as a metabolic regulator. In this study, we aimed to determine the role STAT3 activation in glucose limitation, in leukemia cell lines. K562, NB-4 and HL-60 cells were found sensitive to glucose limitation. In low glucose conditions, total and nuclear STAT3 protein was decreased in all cells. In mitochondria, S727 phosphorylated STAT3 (mitochondrial form) was determined slightly increased in K562 and NB-4 cells. On the other side, ectopically STAT3 expressing cells had increased glucose consumption and less proliferated in low glucose medium. This data suggests that aerobic glycolysis might be upregulated upon STAT3 expression in leukemia cells, in glucose limitation. Furthermore, in this study, it was found that GLUT3 expressing cells did not reduce STAT3 expression in low glucose medium. GLUT3 was previously determined as a molecular marker for cell sensitivity to glucose limitation, therefore, it could be hypothesized as GLUT3 expressing cells might not need to alter STAT3 expression in low glucose level. Overall, our data suggest that leukemia cells rewire glucose metabolism via STAT3 expression in glucose limitation. Elucidating pathways that cause differential phosphorylation of STAT3 and its interaction with other energy regulating pathways in cellular response to glucose limitation might be beneficial to design new drug targets such as STAT3 inhibitors for leukemia treatment.

Aberrant SOCS3 Promoter Methylation as a Noninvasive Diagnostic Biomarker for Locally Advanced Prostate Cancer.

OBJECTIVE: The aim of this study was to investigate the promoter methylation status of Rasassociated domain family 1A (RASSF1A), O-6-methylguanine-DNA methyltransferase (MGMT), Phosphatase with tensin homology (PTEN) and Suppressor of cytokine signaling 3 (SOCS3) tumor suppressor genes and evaluate the clinical utility of these genes as noninvasive, blood-based epigenetic biomarkers for the diagnosis of Prostate Cancer (PCa). METHOD: A total of 41 consecutive patients and 10 healthy control groups were enrolled in the study. Pyrosequencing was performed to analyze the methylation levels of the promoter regions of the four tumor suppressor genes in patients compared to healthy controls. RESULTS: The promoter methylation levels of RASSF1A, MGMT, PTEN and SOCS3 did not differ between the patient and control groups. However, SOCS3 promoter methylation level was significantly higher for patients having locally advanced PCa compared to those having localizedPCa (p<0.05). CONCLUSION: Our results indicated that SOCS3 could be a useful, noninvasive blood-based epigenetic biomarker for the diagnosis of locally advanced PCa.