PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines
The dysregulation of energetic metabolism is one of the hallmarks of cancer cells. Indeed, the growth of head and neck squamous cell carcinoma (HNSCC) cells depends heavily on glycolytic activity, which can be considered a potential therapeutic target. Wnt signaling is one of the pathways that under...
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MDPI AG
2023-11-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/12/599 |
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| author | Robert Kleszcz Jarosław Paluszczak Marta Belka Violetta Krajka-Kuźniak |
| author_facet | Robert Kleszcz Jarosław Paluszczak Marta Belka Violetta Krajka-Kuźniak |
| author_sort | Robert Kleszcz |
| collection | DOAJ |
| description | The dysregulation of energetic metabolism is one of the hallmarks of cancer cells. Indeed, the growth of head and neck squamous cell carcinoma (HNSCC) cells depends heavily on glycolytic activity, which can be considered a potential therapeutic target. Wnt signaling is one of the pathways that undergoes upregulation in HNSCC. Our previous studies have shown that Wnt signaling inhibitors—PRI-724 and IWP-O1—attenuate tongue SCC survival and reduce glucose uptake and lactate release. The aim of this research was to further evaluate the possible mechanisms of the previously observed effects. We assessed the effect of PRI-724 and IWP-O1 on the expression of selected glycolytic enzymes: phosphofructokinase M, pyruvate kinase M2, and lactate dehydrogenase. Relative transcript expression was assessed by real-time PCR, and protein levels by Western blot. Moreover, clinical data concerning mRNA and protein expression, gene promoter methylation, and HNSCC patients’ survival time were analyzed by the UALCAN tool, and protein–protein interaction was assessed using the STRING database. Experimental and bioinformatic data confirmed the relation between Wnt signaling and glycolytic enzymes in tongue cancer cells and HNSCC clinical samples. Overall, the inhibition of glucose metabolism by Wnt signaling inhibitors is a promising mode of action against tongue cancer cells. |
| first_indexed | 2024-03-08T20:53:38Z |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-08T20:53:38Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-593f29a714c14918b20e17fe03f577a42023-12-22T14:00:38ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-11-0145129579959210.3390/cimb45120599PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell LinesRobert Kleszcz0Jarosław Paluszczak1Marta Belka2Violetta Krajka-Kuźniak3Chair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, PolandChair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, PolandChair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, PolandChair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, PolandThe dysregulation of energetic metabolism is one of the hallmarks of cancer cells. Indeed, the growth of head and neck squamous cell carcinoma (HNSCC) cells depends heavily on glycolytic activity, which can be considered a potential therapeutic target. Wnt signaling is one of the pathways that undergoes upregulation in HNSCC. Our previous studies have shown that Wnt signaling inhibitors—PRI-724 and IWP-O1—attenuate tongue SCC survival and reduce glucose uptake and lactate release. The aim of this research was to further evaluate the possible mechanisms of the previously observed effects. We assessed the effect of PRI-724 and IWP-O1 on the expression of selected glycolytic enzymes: phosphofructokinase M, pyruvate kinase M2, and lactate dehydrogenase. Relative transcript expression was assessed by real-time PCR, and protein levels by Western blot. Moreover, clinical data concerning mRNA and protein expression, gene promoter methylation, and HNSCC patients’ survival time were analyzed by the UALCAN tool, and protein–protein interaction was assessed using the STRING database. Experimental and bioinformatic data confirmed the relation between Wnt signaling and glycolytic enzymes in tongue cancer cells and HNSCC clinical samples. Overall, the inhibition of glucose metabolism by Wnt signaling inhibitors is a promising mode of action against tongue cancer cells.https://www.mdpi.com/1467-3045/45/12/599Wnt signalingthe Warburg effectaerobic glycolysishead and neck cancertongue cancerPRI-724 |
| spellingShingle | Robert Kleszcz Jarosław Paluszczak Marta Belka Violetta Krajka-Kuźniak PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines Current Issues in Molecular Biology Wnt signaling the Warburg effect aerobic glycolysis head and neck cancer tongue cancer PRI-724 |
| title | PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines |
| title_full | PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines |
| title_fullStr | PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines |
| title_full_unstemmed | PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines |
| title_short | PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines |
| title_sort | pri 724 and iwp o1 wnt signaling pathway inhibitors modulate the expression of glycolytic enzymes in tongue cancer cell lines |
| topic | Wnt signaling the Warburg effect aerobic glycolysis head and neck cancer tongue cancer PRI-724 |
| url | https://www.mdpi.com/1467-3045/45/12/599 |
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