NTPDase5/PCPH as a New Target in Highly Aggressive Tumors: A Systematic Review

Bracco, Paula A.; Bertoni, Ana Paula Santin; Wink, Márcia Rosângela

doi:10.1155/2014/123010

Cited by 3 publications

(1 citation statement)

References 20 publications

(51 reference statements)

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“…Data were compared by one-way ANOVA, followed by Tukey's test. *p < 0.05 represents statistical significance, comparing K-562 treated with imatinib mesylate for 24 h (K-562 24 h), 48 h (K-562 48 h) and imatinib-resistant K-562 (K-562R) cells to untreated K-562 (K-562) as PCPH [45]. This enzyme presents an important association with the PI3K/PTEN and AKT signaling pathway [46].…”

Section: Discussionmentioning

confidence: 99%

Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line

Willig

Vianna

Beckenkamp

et al. 2020

Purinergic Signalling

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the occurrence of the t(9;22)(q34;q11) translocation. First-line therapy for CML consists of treatment with imatinib mesylate, which selectively inhibits the BCR-ABL protein by competing for its ATP-binding site. Adenine nucleotide signaling is modulated by the ectonucleotidases and this pathway is related to tumorigenic processes. Considering the relationship between ATP and cancer, we aimed to evaluate the influence of imatinib mesylate on the expressions and functions of the NTPDase and ecto-5′-nucleotidase (CD73) enzymes in imatinib-sensitive and -resistant K-562 cell lines. mRNA analysis showed that K-562 cells express all ENTPDs and NT5E. However, when treated with imatinib mesylate for 24 h, the expression of ENTPD1, -2, -3 and -5 increased, leading to a higher nucleotides hydrolysis rate. HPLC analysis identified increased ATP degradation in cells after 24 h of treatment, with consequent ADP and AMP formation, corroborating the increase in gene and protein expression of ectonucleotidases as observed in previous results. On the other hand, we observed that imatinib-resistant K-562 cells presented a decrease in nucleotide hydrolysis and expressions of ENTPD1 and -5. These results suggest an involvement of imatinib in modulating ectonucleotidases in CML that will need further investigation. Since these ectonucleotidases have important catalytic activities in the tumor microenvironment, their modulation in CML cells may represent an important therapeutic approach to regulate levels of extracellular adenine nucleotides.

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Section: Discussionmentioning

confidence: 99%

Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line

Willig

Vianna

Beckenkamp

et al. 2020

Purinergic Signalling

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Is the regulation by miRNAs of NTPDase1 and ecto-5’-nucleotidase genes involved with the different profiles of breast cancer subtypes?

Silva

Neto

Martins

et al. 2021

Purinergic Signalling

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Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns

Brommage

Powell

Vogel

2019

Disease Models &Amp; Mechanisms

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Two large-scale mouse gene knockout phenotyping campaigns have provided extensive data on the functions of thousands of mammalian genes. The ongoing International Mouse Phenotyping Consortium (IMPC), with the goal of examining all ∼20,000 mouse genes, has examined 5115 genes since 2011, and phenotypic data from several analyses are available on the IMPC website (www.mousephenotype.org). Mutant mice having at least one human genetic disease-associated phenotype are available for 185 IMPC genes. Lexicon Pharmaceuticals' Genome5000™ campaign performed similar analyses between 2000 and the end of 2008 focusing on the druggable genome, including enzymes, receptors, transporters, channels and secreted proteins. Mutants (4654 genes, with 3762 viable adult homozygous lines) with therapeutically interesting phenotypes were studied extensively. Importantly, phenotypes for 29 Lexicon mouse gene knockouts were published prior to observations of similar phenotypes resulting from homologous mutations in human genetic disorders. Knockout mouse phenotypes for an additional 30 genes mimicked previously published human genetic disorders. Several of these models have helped develop effective treatments for human diseases. For example, studying Tph1 knockout mice (lacking peripheral serotonin) aided the development of telotristat ethyl, an approved treatment for carcinoid syndrome. Sglt1 (also known as Slc5a1 ) and Sglt2 (also known as Slc5a2 ) knockout mice were employed to develop sotagliflozin, a dual SGLT1/SGLT2 inhibitor having success in clinical trials for diabetes. Clinical trials evaluating inhibitors of AAK1 (neuropathic pain) and SGLT1 (diabetes) are underway. The research community can take advantage of these unbiased analyses of gene function in mice, including the minimally studied ‘ignorome’ genes.

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NTPDase5/PCPH as a New Target in Highly Aggressive Tumors: A Systematic Review

Cited by 3 publications

References 20 publications

Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line

Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line

Is the regulation by miRNAs of NTPDase1 and ecto-5’-nucleotidase genes involved with the different profiles of breast cancer subtypes?

Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns

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