Hexokinase isoenzymes from anaplastic and differentiated medullary thyroid carcinoma in the rat

Rijksen, Gert; Oskam, R.; Molthoff, Carla F. M.; On, Sue-Jin Lee; Streefkerk, M.; Staal, Gerard E.J.

doi:10.1016/0277-5379(84)90172-x

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…Finally, the binding of HK2/VDAC prevents Bax/Bak unbinding from the mitochondria and apoptosis ( 97 , 98 ). Therefore, HK2 seems to be important for sustained cancer growth and has been suggested to be a marker of progression and tumor aggressiveness ( 91 – 103 ).…”

Section: Metabolic Markers In Thyroid Cancermentioning

confidence: 99%

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Metabolic Reprogramming in Thyroid Carcinoma

2018

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Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

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Section: Metabolic Markers In Thyroid Cancermentioning

confidence: 99%

“…The earliest studies documenting the relationship between HK activity and thyroid carcinogenesis date back to the 1980s ( 99 , 103 ). Rijksen et al ( 103 ) showed no differences in HK biochemical characteristics when comparing MTC and ATC. Only the affinity of HK for its substrate was higher in ATC than in MTC.…”

Section: Metabolic Markers In Thyroid Cancermentioning

confidence: 99%

Metabolic Reprogramming in Thyroid Carcinoma

2018

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“…Occasionally, dediffer entiation occurred toward rapidly growing poorly dif ferentiated carcinomas with a scirrhous aspect, which produced only trace amounts of calcitonin (AMTC) [ 15]. In addition, AMTC and DMTC largely differ in their glycolytic rate [18], and in the isozymic compo sition and regulatory properties of key glycolytic en zymes [16,17], Both tumor variants were maintained by subcutaneous transplantation. When tumors had reached a weight of ± 5 g they were surgically re moved under ether anesthesia and stored at -7 0°C for no longer than 3 months.…”

Section: Methodsmentioning

confidence: 99%

Protein Phosphorylation and Tyrosine Kinase Activity in Medullary Thyroid Carcinomas of the Rat

Oskam

Meerendonk²,

Boer³

et al. 1987

Tumor Biol

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The kinetics of endogenous protein phosphorylation and resultant phosphopro-tein patterns were investigated in well-differentiated (DMTC) and undifferentiated (AMTC) medullary thyroid carcinomas of the rat. Cytosolic or particulate fractions from these tumors were incubated with γ-32P-ATP in the presence of various effectors. Phosphorylation appeared to be predominantly independent of exogenously added cyclic AMP. Magnesium and manganese were equally effective cofactors. For both tumor types ³²P incorporation into cytosolic proteins was maximal within 3–4 min after addition of ATP and subsequently decreased gradually within 1 h. In contrast, in particulate preparations maximal incorporation was reached within 30 s and remained constant over a relatively long time span. In both cases, however, ³²P incorporation in extracts from DMTCs were 50–100% higher as compared to AMTCs. Comparison of the phosphoprotein patterns of each tumor after in vitro phosphorylation showed some significant differences. A phosphoprotein with molecular weight of 90 kilodalton (90 kD) was exclusively expressed in the cytosol of DMTC, whereas 99- and 84-kD phosphoproteins were only present in the cytosol of AMTC. The DMTC particulate fraction contained two phosphoproteins (with molecular weights of 40 and 37 kD), which were absent from that of AMTC. In addition, a number of proteins were more intensely phosphorylated in one of the tumors, e.g. proteins of 94 and 33 kD in DMTC cytosol and a protein of 78 kD in AMTC cytosol. Calcium induced phosphorylation of five proteins in DMTC cytosol (with molecular weights of 69, 55, 49, 43 and 32 kD), which were less intensely or not phosphorylated in AMTC. Tyrosine kinase activity was investigated using exogenously added poly(glutamine:tyrosine, 4:1) as an artificial substrate. Cytosolic tyrosine kinase activity in DMTC was ± 50% higher than in AMTC (11.9 ± 0.6 and 8.2 ± 1.7 pmol/mg/min, respectively). The enzyme activities in the paniculate preparations were much higher than in the cytosols ( ± 100 pmol/mg/min), although considerable variations in enzyme activity between different tumors of either type were observed. Quantitative differences in tyrosine kinase activity between AMTC and DMTC particulate fractions did not seem to exist using this substrate. Phosphoamino acid analysis of endogenously phosphorylated proteins in both AMTC and DMTC showed phosphotyrosine to be present only in cytosolic proteins within the 50-kD molecular weight region, the majority of ³²P being on serine and some on threonine. Thus, this study shows that significant differences in protein phosphorylation and tyrosine kinase activity exist between these well-differentiated and undifferentiated carcinomas.

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Type 2 diabetes differentially affects the substrate saturation kinetic attributes of erythrocyte hexokinase and phosphofructokinase

et al. 2019

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The substrate kinetic parameters of hexokinase (HK) and phosphofructokinase (PFK)—the key irreversible enzymes of glycolysis—in erythrocytes from type 2 diabetic subjects were examined in comparison with control subjects. It was observed that the kinetic parameters such as Km, Vmax, Apparent Kcat, Kcat/Km, and substrate (ATP) inhibition kinetic and substrate binding characteristics are significantly altered in the diabetic group. The observed changes are suggestive of compositional changes in the subunit makeup of HK and PFK. The implication of these findings in relation to energy status of the diabetic erythrocyte and its interrelationship with loss of cell deformability are discussed here.

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Hexokinase isoenzymes from anaplastic and differentiated medullary thyroid carcinoma in the rat

Cited by 5 publications

References 13 publications

Metabolic Reprogramming in Thyroid Carcinoma

Metabolic Reprogramming in Thyroid Carcinoma

Protein Phosphorylation and Tyrosine Kinase Activity in Medullary Thyroid Carcinomas of the Rat

Type 2 diabetes differentially affects the substrate saturation kinetic attributes of erythrocyte hexokinase and phosphofructokinase

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