The Experts below are selected from a list of 14550 Experts worldwide ranked by ideXlab platform
Zhijun Min - One of the best experts on this subject based on the ideXlab platform.
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The SIRT6-Autophagy-Warburg Effect Axis in Papillary Thyroid Cancer.
Frontiers in oncology, 2020Co-Authors: Zhou Yang, Renhong Huang, Xiyi Wei, Zhijun MinAbstract:As shown in our previous study, SIRT6 promotes an aggressive phenotype and the epithelial-mesenchymal transition (EMT) in papillary thyroid cancer (PTC). In this study, we focused on the regulatory axis including SIRT6, autophagy, and the Warburg Effect. We innovatively confirmed that SIRT6 overexpression depleted histone H3 lysine 56 acetylation (H3K56ac) of the negative regulator of reactive oxygen species (NRROS) in vitro, thus increasing reactive oxygen species (ROS) production. The accumulated ROS then activated endoplasmic reticulum stress (ER stress) and subsequently induced autophagy. Furthermore, SIRT6 overexpression inhibited glucose transporter 1 (GLUT1) via autophagy-mediated degradation, ultimately suppressing the Warburg Effect. Treatment with the ROS scavenger N-acetyl-L-cysteine (NAC, 5 mM) or the autophagy inhibitor chloroquine (CQ) both rescued the inhibition of the Warburg Effect. Additionally, a higher concentration of NAC (15 mM) further inhibited the Warburg Effect. These concentration-dependent bilateral Effects of NAC on this process were confirmed to be due to the regulation of the AMPK signaling pathway. Finally, we further examined this mechanism in vivo by establishing subcutaneous xenografts in nude mice and analyzed the tumors using 18F radio-labeled fluorodeoxyglucose (18F-FDG) PET/CT. In conclusion, we identified a SIRT6-ROS-ER stress-autophagy-GLUT1-Warburg Effect axis in PTC, which may provide a new therapeutic target. In addition, NAC (low concentration) and CQ, previously considered to be tumor inhibitors, were shown to promote tumorigenesis in PTC with high SIRT6 expression by inducing the Warburg Effect.
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SIRT6-Autophagy-Warburg Effect axis in papillary thyroid cancer
2020Co-Authors: Zhou Yang, Renhong Huang, Zhijun MinAbstract:Abstract Background: Our previous study has demonstrated SIRT6 promotes aggression and epithelial-mesenchymal transition (EMT) in papillary thyroid cancer (PTC). In this study, we focused on the regulatory axis between SIRT6-Autophagy-Warburg Effect.Methods: Autophagy activation was confirmed by Western Blotting, quantitative PCR, immunofluorescence and transmission electron microscopy. Warburg Effect was examined by Seahorse XF96 analysis and PET imaging. Regulation of SIRT6 in negatively regulates reactive oxygen species (NRROS) was confirmed by chromatin immunoprecipitation.Results: We innovatively confirmed overexpression of SIRT6 depleted histone H3 lysine 56 acetylation (H3K56ac) of NRROS in vitro, thus increased reactive oxygen species (ROS). Then, accumulated ROS activated endoplasmic reticulum stress (ER stress), and subsequently induced autophagy. Furthermore, the overexpression of SIRT6 inhibited Glucose Transporter 1 (Glut1) via autophagic degradation, thus ulteriorly suppressed Warburg Effect. Treatment of ROS scavenger N-acetyl-L-cysteine (NAC, 5mM) or autophagy inhibitor chloroquine (CQ) both rescued the inhibition of Warburg Effect. In addition, higher concentration of NAC (15mM) deepened the inhibited Warburg Effect. This concentration-dependent bilateral Effects of NAC in this process had been confirmed owe to regulation of AMPK signaling pathway. Finally, we further determined above mechanism in vivo via subcutaneous xenografts in nude mice applied with 18F-FDG PET/CT.Conclusions: We identified a SIRT6-ROS-ERstress-Autophagy-Glut1-Warburg Effect axis in PTC, which may provide new target for therapy. In addition, NAC (low concentration) and CQ which previously been considered as tumor inhibitors, have been shown to promote tumorigenesis in PTC with high SIRT6 expression via activation of Warburg Effect.
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SIRT6 promotes the Warburg Effect of papillary thyroid cancer cell BCPAP through reactive oxygen species.
OncoTargets and therapy, 2019Co-Authors: Zhou Yang, Renhong Huang, Zhijun MinAbstract:Purpose: Our previous study demonstrated that SIRT6 is upregulated in papillary thyroid cancer (PTC) and enhances tumor aggressiveness. In this study, we further researched its influence in the Warburg Effect. Methods: SIRT6-upregulated and downregulated BCPAP cells and negative control BCPAP-NC groups were generated with lentiviral vectors. In these two cell lines, reactive oxygen species (ROS) were detected by dichlorodihydrofluorescein diacetate. Expression of the key Warburg Effect genes including GLUT1, HK2, GAPDH, PGK1, ENO1, PKM2 and LDHA was measured by quantitative real-time PCR and western blotting. Glucose uptake, lactate production and the ATP content of cells were detected with assay kits. The ROS scavenger N-acetylcysteine was used for treatment of BCPAP-SIRT6, and the same measurements as described above were detected again. Results: Compared with the BCPAP-NC group, expression of the key Warburg Effect genes including Glut1, HK2 and GAPDH and their protein products was upregulated in the BCPAP-SIRT6 group, whereas BCPAP-shSIRT6 showed significant downregulation. Meanwhile, ROS, glucose uptake, lactate production and ATP content of the BCPAP-SIRT6 group were also significantly increased, and BCPAP-shSIRT6 showed significant downregulation. Furthermore, upregulation of key Warburg Effect genes and glucose uptake, lactate production and ATP content were all rescued after treatment with ROS scavenger. Conclusion: SIRT6 promoted the Warburg Effect of PTC cells via upregulation of ROS. Inhibition of ROS in SIRT6-upregulated cells could rescue activation of the Warburg Effect.
Marco G Alves - One of the best experts on this subject based on the ideXlab platform.
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the Warburg Effect revisited lesson from the sertoli cell
Medicinal Research Reviews, 2015Co-Authors: Pedro Oliveira, Ana D Martins, Ana Catarina Moreira, Yan C Cheng, Marco G AlvesAbstract:Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism. The Warburg Effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a "Warburg-like" metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and Effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear "Warburg-like" metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg Effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg Effect and cell proliferation.
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The Warburg Effect Revisited—Lesson from the Sertoli Cell
Medicinal research reviews, 2014Co-Authors: Pedro Oliveira, Ana D Martins, Ana Catarina Moreira, C. Yan Cheng, Marco G AlvesAbstract:Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism. The Warburg Effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a "Warburg-like" metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and Effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear "Warburg-like" metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg Effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg Effect and cell proliferation.
Zhou Yang - One of the best experts on this subject based on the ideXlab platform.
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The SIRT6-Autophagy-Warburg Effect Axis in Papillary Thyroid Cancer.
Frontiers in oncology, 2020Co-Authors: Zhou Yang, Renhong Huang, Xiyi Wei, Zhijun MinAbstract:As shown in our previous study, SIRT6 promotes an aggressive phenotype and the epithelial-mesenchymal transition (EMT) in papillary thyroid cancer (PTC). In this study, we focused on the regulatory axis including SIRT6, autophagy, and the Warburg Effect. We innovatively confirmed that SIRT6 overexpression depleted histone H3 lysine 56 acetylation (H3K56ac) of the negative regulator of reactive oxygen species (NRROS) in vitro, thus increasing reactive oxygen species (ROS) production. The accumulated ROS then activated endoplasmic reticulum stress (ER stress) and subsequently induced autophagy. Furthermore, SIRT6 overexpression inhibited glucose transporter 1 (GLUT1) via autophagy-mediated degradation, ultimately suppressing the Warburg Effect. Treatment with the ROS scavenger N-acetyl-L-cysteine (NAC, 5 mM) or the autophagy inhibitor chloroquine (CQ) both rescued the inhibition of the Warburg Effect. Additionally, a higher concentration of NAC (15 mM) further inhibited the Warburg Effect. These concentration-dependent bilateral Effects of NAC on this process were confirmed to be due to the regulation of the AMPK signaling pathway. Finally, we further examined this mechanism in vivo by establishing subcutaneous xenografts in nude mice and analyzed the tumors using 18F radio-labeled fluorodeoxyglucose (18F-FDG) PET/CT. In conclusion, we identified a SIRT6-ROS-ER stress-autophagy-GLUT1-Warburg Effect axis in PTC, which may provide a new therapeutic target. In addition, NAC (low concentration) and CQ, previously considered to be tumor inhibitors, were shown to promote tumorigenesis in PTC with high SIRT6 expression by inducing the Warburg Effect.
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SIRT6-Autophagy-Warburg Effect axis in papillary thyroid cancer
2020Co-Authors: Zhou Yang, Renhong Huang, Zhijun MinAbstract:Abstract Background: Our previous study has demonstrated SIRT6 promotes aggression and epithelial-mesenchymal transition (EMT) in papillary thyroid cancer (PTC). In this study, we focused on the regulatory axis between SIRT6-Autophagy-Warburg Effect.Methods: Autophagy activation was confirmed by Western Blotting, quantitative PCR, immunofluorescence and transmission electron microscopy. Warburg Effect was examined by Seahorse XF96 analysis and PET imaging. Regulation of SIRT6 in negatively regulates reactive oxygen species (NRROS) was confirmed by chromatin immunoprecipitation.Results: We innovatively confirmed overexpression of SIRT6 depleted histone H3 lysine 56 acetylation (H3K56ac) of NRROS in vitro, thus increased reactive oxygen species (ROS). Then, accumulated ROS activated endoplasmic reticulum stress (ER stress), and subsequently induced autophagy. Furthermore, the overexpression of SIRT6 inhibited Glucose Transporter 1 (Glut1) via autophagic degradation, thus ulteriorly suppressed Warburg Effect. Treatment of ROS scavenger N-acetyl-L-cysteine (NAC, 5mM) or autophagy inhibitor chloroquine (CQ) both rescued the inhibition of Warburg Effect. In addition, higher concentration of NAC (15mM) deepened the inhibited Warburg Effect. This concentration-dependent bilateral Effects of NAC in this process had been confirmed owe to regulation of AMPK signaling pathway. Finally, we further determined above mechanism in vivo via subcutaneous xenografts in nude mice applied with 18F-FDG PET/CT.Conclusions: We identified a SIRT6-ROS-ERstress-Autophagy-Glut1-Warburg Effect axis in PTC, which may provide new target for therapy. In addition, NAC (low concentration) and CQ which previously been considered as tumor inhibitors, have been shown to promote tumorigenesis in PTC with high SIRT6 expression via activation of Warburg Effect.
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SIRT6 promotes the Warburg Effect of papillary thyroid cancer cell BCPAP through reactive oxygen species.
OncoTargets and therapy, 2019Co-Authors: Zhou Yang, Renhong Huang, Zhijun MinAbstract:Purpose: Our previous study demonstrated that SIRT6 is upregulated in papillary thyroid cancer (PTC) and enhances tumor aggressiveness. In this study, we further researched its influence in the Warburg Effect. Methods: SIRT6-upregulated and downregulated BCPAP cells and negative control BCPAP-NC groups were generated with lentiviral vectors. In these two cell lines, reactive oxygen species (ROS) were detected by dichlorodihydrofluorescein diacetate. Expression of the key Warburg Effect genes including GLUT1, HK2, GAPDH, PGK1, ENO1, PKM2 and LDHA was measured by quantitative real-time PCR and western blotting. Glucose uptake, lactate production and the ATP content of cells were detected with assay kits. The ROS scavenger N-acetylcysteine was used for treatment of BCPAP-SIRT6, and the same measurements as described above were detected again. Results: Compared with the BCPAP-NC group, expression of the key Warburg Effect genes including Glut1, HK2 and GAPDH and their protein products was upregulated in the BCPAP-SIRT6 group, whereas BCPAP-shSIRT6 showed significant downregulation. Meanwhile, ROS, glucose uptake, lactate production and ATP content of the BCPAP-SIRT6 group were also significantly increased, and BCPAP-shSIRT6 showed significant downregulation. Furthermore, upregulation of key Warburg Effect genes and glucose uptake, lactate production and ATP content were all rescued after treatment with ROS scavenger. Conclusion: SIRT6 promoted the Warburg Effect of PTC cells via upregulation of ROS. Inhibition of ROS in SIRT6-upregulated cells could rescue activation of the Warburg Effect.
Christos Samakovlis - One of the best experts on this subject based on the ideXlab platform.
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a rassf1a hif1α loop drives Warburg Effect in cancer and pulmonary hypertension
Nature Communications, 2019Co-Authors: Swati Dabral, Gregg L Semenza, Christian Muecke, Chanil Valasarajan, Mario Schmoranzer, Astrid Wietelmann, Michael Meister, Thomas Muley, Tamina Seegernukpezah, Christos SamakovlisAbstract:Hypoxia signaling plays a major role in non-malignant and malignant hyperproliferative diseases. Pulmonary hypertension (PH), a hypoxia-driven vascular disease, is characterized by a glycolytic switch similar to the Warburg Effect in cancer. Ras association domain family 1A (RASSF1A) is a scaffold protein that acts as a tumour suppressor. Here we show that hypoxia promotes stabilization of RASSF1A through NOX-1- and protein kinase C- dependent phosphorylation. In parallel, hypoxia inducible factor-1 α (HIF-1α) activates RASSF1A transcription via HIF-binding sites in the RASSF1A promoter region. Vice versa, RASSF1A binds to HIF-1α, blocks its prolyl-hydroxylation and proteasomal degradation, and thus enhances the activation of the glycolytic switch. We find that this mechanism operates in experimental hypoxia-induced PH, which is blocked in RASSF1A knockout mice, in human primary PH vascular cells, and in a subset of human lung cancer cells. We conclude that RASSF1A-HIF-1α forms a feedforward loop driving hypoxia signaling in PH and cancer. Pulmonary hypertension is characterized by a metabolic switch similar to the Warburg Effect in cancer. Here Dabral et al. describe a RASSF1a-HIF-1α feedforward loop driving the Warburg Effect both in a mouse model of hypoxia-induced pulmonary hypertension and a subset of human cancer cells.
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A RASSF1A-HIF1α loop drives Warburg Effect in cancer and pulmonary hypertension
Nature Publishing Group, 2019Co-Authors: Swati Dabral, Gregg L Semenza, Christian Muecke, Chanil Valasarajan, Mario Schmoranzer, Astrid Wietelmann, Michael Meister, Thomas Muley, Tamina Seeger-nukpezah, Christos SamakovlisAbstract:Pulmonary hypertension is characterized by a metabolic switch similar to the Warburg Effect in cancer. Here Dabral et al. describe a RASSF1a-HIF-1α feedforward loop driving the Warburg Effect both in a mouse model of hypoxia-induced pulmonary hypertension and a subset of human cancer cells
Pedro Oliveira - One of the best experts on this subject based on the ideXlab platform.
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the Warburg Effect revisited lesson from the sertoli cell
Medicinal Research Reviews, 2015Co-Authors: Pedro Oliveira, Ana D Martins, Ana Catarina Moreira, Yan C Cheng, Marco G AlvesAbstract:Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism. The Warburg Effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a "Warburg-like" metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and Effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear "Warburg-like" metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg Effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg Effect and cell proliferation.
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The Warburg Effect Revisited—Lesson from the Sertoli Cell
Medicinal research reviews, 2014Co-Authors: Pedro Oliveira, Ana D Martins, Ana Catarina Moreira, C. Yan Cheng, Marco G AlvesAbstract:Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism. The Warburg Effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a "Warburg-like" metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and Effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear "Warburg-like" metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg Effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg Effect and cell proliferation.
