Dataset Information

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation.

ABSTRACT: Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potential targets in cancer therapy. In this work, we aimed to evaluate the role of sedoheptulose kinase (SHPK), a key regulator of carbon flux that catalyzes the phosphorylation of sedoheptulose in the nonoxidative arm of the PPP. SHPK expression was investigated in patients with GBM using microarray data. SHPK was also overexpressed in GBM cells, and functional studies were conducted. SHPK expression in GBM shows a significant correlation with histology, prognosis, and survival. In particular, its increased expression is associated with a worse prognosis. Furthermore, its overexpression in GBM cells confirms an increase in cell proliferation. This work highlights for the first time the importance of SHPK in GBM for tumor progression and proposes this enzyme and the nonoxidative PPP as possible therapeutic targets.

SUBMITTER: Franceschi S

PROVIDER: S-EPMC9180619 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation.

Franceschi Sara S Lessi Francesca F Morelli Mariangela M Menicagli Michele M Pasqualetti Francesco F Aretini Paolo P Mazzanti Chiara Maria CM

International journal of molecular sciences 20220526 11

Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potentia ...[more]

PMID: 35682658

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Project description:Sinorhizobium meliloti is a Gram-negative alphaproteobacterium that can enter into a symbiotic relationship with Medicago sativa and Medicago truncatula Previous work determined that a mutation in the tkt2 gene, which encodes a putative transketolase, could prevent medium acidification associated with a mutant strain unable to metabolize galactose. Since the pentose phosphate pathway in S. meliloti is not well studied, strains carrying mutations in either tkt2 and tal, which encodes a putative transaldolase, were characterized. Carbon metabolism phenotypes revealed that both mutants were impaired in growth on erythritol and ribose. This phenotype was more pronounced for the tkt2 mutant strain, which also displayed auxotrophy for aromatic amino acids. Changes in pentose phosphate pathway metabolite concentrations were also consistent with a mutation in either tkt2 or tal The concentrations of metabolites in central carbon metabolism were also found to shift dramatically in strains carrying a tkt2 mutation. While the concentrations of proteins involved in central carbon metabolism did not change significantly under any conditions, the levels of those associated with iron acquisition increased in the wild-type strain with erythritol induction. These proteins were not detected in either mutant, resulting in less observable rhizobactin production in the tkt2 mutant. While both mutants were impaired in succinoglycan synthesis, only the tkt2 mutant strain was unable to establish symbiosis with alfalfa. These results suggest that tkt2 and tal play central roles in regulating the carbon flow necessary for carbon metabolism and the establishment of symbiosis.IMPORTANCESinorhizobium meliloti is a model organism for the study of plant-microbe interactions and metabolism, especially because it effects nitrogen fixation. The ability to derive the energy necessary for nitrogen fixation is dependent on an organism's ability to metabolize carbon efficiently. The pentose phosphate pathway is central in the interconversion of hexoses and pentoses. This study characterizes the key enzymes of the nonoxidative branch of the pentose phosphate pathway by using defined genetic mutations and shows the effects the mutations have on the metabolite profile and on physiological processes such as the biosynthesis of exopolysaccharide, as well as the ability to regulate iron acquisition.

Dataset Information

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation.

Publications

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation.

Similar Datasets

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