Mojgan Mergny - Academia.edu (original) (raw)
Papers by Mojgan Mergny
Supplementary Materials, Figures 1-5 from Disruption of Sphingosine 1-Phosphate Lyase Confers Res... more Supplementary Materials, Figures 1-5 from Disruption of Sphingosine 1-Phosphate Lyase Confers Resistance to Chemotherapy and Promotes Oncogenesis through Bcl-2/Bcl-xL Upregulation
This manuscript has been published online, prior to printing for Autophagy, Volume 2, Issue 2. De... more This manuscript has been published online, prior to printing for Autophagy, Volume 2, Issue 2. Definitive page numbers have not been assigned. The current citation is:
Cells, 2021
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer ... more Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer cell types, but also leads to the activation of signaling pathways that favor resistance to cell death. Here, we investigated the as yet unknown roles of calcium signaling and autophagy regulatory proteins during TRAIL-induced cell death in leukemia cells. Taking advantage of the Gene Expression Profiling Interactive Analysis (GEPIA) project, we first found that leukemia patients present a unique TRAIL receptor gene expression pattern that may reflect their resistance to TRAIL. The exposure of NB4 acute promyelocytic leukemia cells to TRAIL induces intracellular Ca2+ influx through a calcium release-activated channel (CRAC)-dependent mechanism, leading to an anti-apoptotic response. Mechanistically, we showed that upon TRAIL treatment, two autophagy proteins, ATG7 and p62/SQSTM1, are recruited to the death-inducing signaling complex (DISC) and are essential for TRAIL-induced Ca2+ influx ...
Cells, 2021
Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death a... more Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death and differentiation. Here, we investigated the impact of Ca2+ in regulating acute promyelocytic leukemia (APL) cell fate in response to the anti-cancer agent all-trans retinoic acid (ATRA). We observed that ATRA promotes calcium entry through store-operated calcium (SOC) channels into acute promyelocytic leukemia (APL) cells. This response is associated with changes in the expression profiles of ORAI1 and STIM1, two proteins involved in SOC channels activation, as well as with a significant upregulation of several key proteins associated to calcium signaling. Moreover, ATRA treatment of APL cells led to a significant activation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and its downstream effector AMP-activated protein kinase (AMPK), linking Ca2+ signaling to autophagy. Pharmacological inhibition of SOC channels and CAMKK2 enhanced ATRA-induced cell differentiation a...
PLOS Pathogens, 2019
Humans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin a... more Humans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin and Cytolethal Distending Toxin (CDT), the latter being secreted by many pathogenic bacteria. Our aim was to evaluate the effects induced by these genotoxins on nuclear remodeling in the context of cell survival. Helicobacter infected mice, coculture experiments with CDT-and colibactin-secreting bacteria and hepatic, intestinal and gastric cells, and xenograft mouse-derived models were used to assess the nuclear remodeling in vitro and in vivo. Our results showed that CDT and colibactin induced-nuclear remodeling can be associated with the formation of deep cytoplasmic invaginations in the nucleus of giant cells. These structures, observed both in vivo and in vitro, correspond to nucleoplasmic reticulum (NR). The core of the NR was found to concentrate ribosomes, proteins involved in mRNA translation, polyadenylated RNA and the main components of the complex mCRD involved in mRNA turnover. These structures are active sites of mRNA translation, correlated with a high degree of ploidy, and involve MAPK and calcium signaling. Additional data show that insulation and concentration of these adaptive ribonucleoprotein particles within the nucleus are dynamic, transient and protect the cell until the genotoxic stress is relieved. Bacterial genotoxins-induced NR would be a privileged gateway for selected mRNA to be preferably transported therein for local translation. These findings offer new insights into the context of NR formation, a common feature of many cancers, which not only appears in response to therapies-induced DNA damage but also earlier in response to genotoxic bacteria.
International Journal of Molecular Sciences, 2019
Autophagy is one of the main cellular catabolic pathways controlling a variety of physiological p... more Autophagy is one of the main cellular catabolic pathways controlling a variety of physiological processes, including those involved in self-renewal, differentiation and death. While acute promyelocytic leukemia (APL) cells manifest low levels of expression of autophagy genes associated with reduced autophagy activity, the introduction of all-trans retinoid acid (ATRA)—a differentiating agent currently used in clinical settings—restores autophagy in these cells. ATRA-induced autophagy is involved in granulocytes differentiation through a mechanism that involves among others the degradation of the PML-RARα oncoprotein. Arsenic trioxide (ATO) is another anti-cancer agent that promotes autophagy-dependent clearance of promyelocytic leukemia retinoic acid receptor alpha gene (PML-RARα) in APL cells. Hence, enhancing autophagy may have therapeutic benefits in maturation-resistant APL cells. However, the role of autophagy in response to APL therapy is not so simple, because some autophagy ...
Molecular & Cellular Oncology, 2019
![Research paper thumbnail of [The yin and the yang of autophagy in cancer cells]](https://attachments.academia-assets.com/115975419/thumbnails/1.jpg)
](Medecine sciences : M/S, 2017
Autophagy is a self-cannibalism process essential for tissue homeostasis, which can be activated ... more Autophagy is a self-cannibalism process essential for tissue homeostasis, which can be activated following different environmental stressful conditions. In normal cells, autophagy could act as a brake to prevent tumorigenesis, but cancer cells are able to hijack this process to their own benefit, to promote tumor growth and/or tumor resistance to anti-cancer therapies. Scientists and clinicians attempt to modulate this process to improve therapies, using autophagy inhibitors or activators, some of them being tested currently in clinical trials against several types of tumors. Thus, it appears that autophagy is at the center of a showdown between cancer cells and anti-cancer therapies. In this review, we focus on the mechanisms by which autophagy could be either the yin or the yang of cancers.
Autophagy Networks in Inflammation, 2016
The homeostasis between the oxidant and antioxidant levels in cells is altered in several disease... more The homeostasis between the oxidant and antioxidant levels in cells is altered in several diseases including cancer, neurodegenerative diseases, and inflammatory disorders. Macroautophagy (hereafter referred to as autophagy) is a redox (reduction/oxidation)-sensitive process that results in degradation of cellular constituents such as proteins, lipids, and mitochondria through the lysosomal pathway. There is a complex and mutual relationship between pathways that control levels of reactive oxygen species (ROS) and autophagy. Autophagy is activated by various stimuli in cells and ROS are one of these autophagy inducers. The accumulation of ROS induces autophagy both by direct effect on the core autophagy machinery and by indirect influence on the components of the autophagy-regulatory signaling pathway. In turn, autophagy regulates the abundance of ROS in cells by promoting the clearance of damaged mitochondria and oxidized cellular substrates and by modulating activity of the detoxifying antioxidant systems. ROS are also involved in the initiation of inflammation, a process that required the secretion of several inflammatory mediators. Here, we will discuss the regulation of inflammatory responses by autophagy as a consequence of the interplay of autophagy and ROS signaling pathways.
Cellular Microbiology, 2016
Cytotoxicity of many plant and bacterial toxins requires their endocytosis and retrograde transpo... more Cytotoxicity of many plant and bacterial toxins requires their endocytosis and retrograde transport from endosomes to the endoplasmic reticulum. Using cell fractionation and immunoblotting procedures, we have assessed the fate and action of the plant toxin ricin in rat liver in vivo, focusing on endosome-associated events and induction of apoptosis. Injected ricin rapidly accumulated in endosomes as an intact A/B heterodimer (5-90 min) and was later (15-90 min) partially translocated to cytosol as A-and B-chains. Unlike cholera and diphtheria toxins, which also undergo endocytosis in liver, neither in cell-free endosomes loaded by ricin in vivo nor upon incubation with endosomal lysates did ricin undergo degradation in vitro. A time-dependent translocation of ricin across the endosomal membrane occurred in cell-free endosomes. Endosome-located thioredoxin reductase-1 was required for translocation as shown by its physical association with ricin chains and effects of its removal and inhibition. Ricin induced in vivo intrinsic apoptosis as judged by increased cytochrome c content, activation of caspase-9 and caspase-3, and enrichment of DNA fragments in cytosol. Furthermore, reduced ricin and ricin B-chain caused cytochrome c release from mitochondria in vivo and in vitro, suggesting that the interaction of ricin B-chain with mitochondria is involved in ricin-induced apoptosis.
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, 2016
Autophagy (a Greek term meaning self-digestion) and apoptosis (a Greek term meaning “falling off”... more Autophagy (a Greek term meaning self-digestion) and apoptosis (a Greek term meaning “falling off”) constitute two distinct evolutionarily conserved processes that are involved in tissue homeostasis in metazoans. Dysfunction of one of both processes can result in development of human pathologies including cancer, neurodegenerative diseases, or inflammatory-related diseases. Autophagy and apoptosis share several signaling pathways and can mutually regulate each other to ensure cellular homeostasis in response to a given stress signal. Although autophagy has been often considered as a survival mechanism, a body of evidence reveals that autophagy can contribute to both caspase-dependent and caspase-independent programmed cell death. In this chapter, we summarize our current understanding of the molecular interplay between autophagy and death receptor signaling pathways and discuss how autophagy and autophagy-regulatory proteins can control receptor-mediated cell death signaling.
Biochemical Journal, 1994
The effects of u.v. A radiations on phospholipid synthesis were studied in the N.C.T.C. 2544 huma... more The effects of u.v. A radiations on phospholipid synthesis were studied in the N.C.T.C. 2544 human keratinocyte cell line, by using [14C]arachidonic acid, [14C]oleic acid or sodium [32P]orthophosphate as precursors. Cells were irradiated in Hanks' medium with 365 nm light at doses up to 19 J/cm2, and then phospholipid synthesis from the three precursors was studied. Under these conditions, only small alterations in the incorporation pattern of [14C]arachidonic into phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI)] were observed, for u.v. A irradiation doses up to 19 J/cm2. In contrast, with [14C]oleic acid as precursor, two additional spots were observed, which co-migrate with pure phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG) standards. The incorporation of [14C]oleic acid into PG and DPG was decreased in a dose-dependent manner after u.v. A exposure, with about 50% and 75% decreases at 9.5 J/cm2 and 19 J/cm2 resp...
Autophagy, 2015
activated protein kinase 8; MAP1LC3, microtubule-associated protein 1 light chain 3; MTOR, mechan... more activated protein kinase 8; MAP1LC3, microtubule-associated protein 1 light chain 3; MTOR, mechanistic target of rapamycin; MTORC1, mechanistic target of rapamycin complex 1; MTORC2, mechanistic target of rapamycin complex 2; NADPH, nicotinamide adenine dinucleotide phosphate; SQSTM1/p62, sequestosome 1; EGLN/PHD, egl-9 family hypoxia-inducible factor; RB1CC1/FIP200, RB1-inducible coiled-coil 1; RRAG, Ras-related GTP binding; RHEB, RAS homolog enriched in brain; ROS, reactive oxygen species; SLC1A5, solute carrier family 1 (neutral amino acid transporter) member 5; SLC7A5, solute carrier family 7 (amino acid transporter light chain, L system), member 5; SLC3A2, solute carrier family 3 (amino acid transporter heavy chain), member 2; TCA, tricarboxyic acid; TFEB, transcription factor EB; TSC, tuberous sclerosis; ULK1/2, unc-51 like autophagy activating kinase 1/2. The remarkable metabolic differences between cancer cells and normal cells result in the potential for targeted cancer therapy. The upregulation of glutaminolysis provides energetic advantages to cancer cells. The recently described link between glutaminolysis and autophagy, mediated by MTORC1, may constitute an attractive target for therapeutic strategies. A combination of therapies targeting simultaneously cell signaling, cancer metabolism, and autophagy can solve therapy resistance and tumor relapse problems, commonly observed in patients treated with most of the current targeted therapies. In this review we summarize the mechanistic link between glutaminolysis and autophagy, and discuss the impacts of these processes on cancer progression and the potential for therapeutic intervention.
American journal of cancer research, 2011
Tight regulation of both the NF-κB pathway and the autophagy process is necessary for maintenance... more Tight regulation of both the NF-κB pathway and the autophagy process is necessary for maintenance of cellular homeostasis. Deregulation of both pathways is frequently observed in cancer cells and is associated with tumorigenesis and tumor cell resistance to cancer therapies. Autophagy is involved in several cellular functions regulated by NF-κB including cell survival, differentiation, senescence, inflammation, and immunity. On a molecular level, autophagy and NF-κB share common upstream signals and regulators and can control each other through positive or negative feedback loops, thus ensuring homeostatic responses. Here, we summarize and discuss the most recent discoveries that shed new light on the complex interplay between autophagy and NF-κB signaling pathways; this certainly has functional relevance in tumorigenesis and tumor responses to therapy.
Cancer Drug Discovery and Development
... J Cell Sci 2006; 119:259–270. 52. Møller MT, Samari HR, Holden L, Seglen PO. Regulation of ma... more ... J Cell Sci 2006; 119:259–270. 52. Møller MT, Samari HR, Holden L, Seglen PO. Regulation of mammalian autophagy by protein phosphorylation. In: Klionsky DJ, ed. Autophagy. Georgetown, TX: Landes Bioscience 2004; 49–59. 53. ...
Autophagy, 2006
The downregulation of macroautophagy observed in cancer cells is associated with tumor progressio... more The downregulation of macroautophagy observed in cancer cells is associated with tumor progression. The regulation of macroautophagy by signaling pathways overlaps with the control of cell growth, proliferation, cell survival and death. Several tumor suppressor genes (PTEN, TSC2 and p53) involved in the mTOR signaling network have been shown to stimulate autophagy. In contrast, the oncoproteins involved in this network have the opposite effect. These findings, together with the discovery that haploinsufficiency of the tumor suppressor beclin 1 promotes tumorigenesis in various tissues in transgenic mice, give credibility to the idea that autophagy is a tumor suppressor mechanism. The induction of macroautophagy by cancer treatments may also contribute to cell eradication. However, cancer cells sometimes mobilize autophagic capacities in response to various stimuli without a fatal outcome, suggesting that they can also exploit macroautophagy for their own benefit.
Supplementary Materials, Figures 1-5 from Disruption of Sphingosine 1-Phosphate Lyase Confers Res... more Supplementary Materials, Figures 1-5 from Disruption of Sphingosine 1-Phosphate Lyase Confers Resistance to Chemotherapy and Promotes Oncogenesis through Bcl-2/Bcl-xL Upregulation
This manuscript has been published online, prior to printing for Autophagy, Volume 2, Issue 2. De... more This manuscript has been published online, prior to printing for Autophagy, Volume 2, Issue 2. Definitive page numbers have not been assigned. The current citation is:
Cells, 2021
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer ... more Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer cell types, but also leads to the activation of signaling pathways that favor resistance to cell death. Here, we investigated the as yet unknown roles of calcium signaling and autophagy regulatory proteins during TRAIL-induced cell death in leukemia cells. Taking advantage of the Gene Expression Profiling Interactive Analysis (GEPIA) project, we first found that leukemia patients present a unique TRAIL receptor gene expression pattern that may reflect their resistance to TRAIL. The exposure of NB4 acute promyelocytic leukemia cells to TRAIL induces intracellular Ca2+ influx through a calcium release-activated channel (CRAC)-dependent mechanism, leading to an anti-apoptotic response. Mechanistically, we showed that upon TRAIL treatment, two autophagy proteins, ATG7 and p62/SQSTM1, are recruited to the death-inducing signaling complex (DISC) and are essential for TRAIL-induced Ca2+ influx ...
Cells, 2021
Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death a... more Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death and differentiation. Here, we investigated the impact of Ca2+ in regulating acute promyelocytic leukemia (APL) cell fate in response to the anti-cancer agent all-trans retinoic acid (ATRA). We observed that ATRA promotes calcium entry through store-operated calcium (SOC) channels into acute promyelocytic leukemia (APL) cells. This response is associated with changes in the expression profiles of ORAI1 and STIM1, two proteins involved in SOC channels activation, as well as with a significant upregulation of several key proteins associated to calcium signaling. Moreover, ATRA treatment of APL cells led to a significant activation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and its downstream effector AMP-activated protein kinase (AMPK), linking Ca2+ signaling to autophagy. Pharmacological inhibition of SOC channels and CAMKK2 enhanced ATRA-induced cell differentiation a...
PLOS Pathogens, 2019
Humans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin a... more Humans are frequently exposed to bacterial genotoxins involved in digestive cancers, colibactin and Cytolethal Distending Toxin (CDT), the latter being secreted by many pathogenic bacteria. Our aim was to evaluate the effects induced by these genotoxins on nuclear remodeling in the context of cell survival. Helicobacter infected mice, coculture experiments with CDT-and colibactin-secreting bacteria and hepatic, intestinal and gastric cells, and xenograft mouse-derived models were used to assess the nuclear remodeling in vitro and in vivo. Our results showed that CDT and colibactin induced-nuclear remodeling can be associated with the formation of deep cytoplasmic invaginations in the nucleus of giant cells. These structures, observed both in vivo and in vitro, correspond to nucleoplasmic reticulum (NR). The core of the NR was found to concentrate ribosomes, proteins involved in mRNA translation, polyadenylated RNA and the main components of the complex mCRD involved in mRNA turnover. These structures are active sites of mRNA translation, correlated with a high degree of ploidy, and involve MAPK and calcium signaling. Additional data show that insulation and concentration of these adaptive ribonucleoprotein particles within the nucleus are dynamic, transient and protect the cell until the genotoxic stress is relieved. Bacterial genotoxins-induced NR would be a privileged gateway for selected mRNA to be preferably transported therein for local translation. These findings offer new insights into the context of NR formation, a common feature of many cancers, which not only appears in response to therapies-induced DNA damage but also earlier in response to genotoxic bacteria.
International Journal of Molecular Sciences, 2019
Autophagy is one of the main cellular catabolic pathways controlling a variety of physiological p... more Autophagy is one of the main cellular catabolic pathways controlling a variety of physiological processes, including those involved in self-renewal, differentiation and death. While acute promyelocytic leukemia (APL) cells manifest low levels of expression of autophagy genes associated with reduced autophagy activity, the introduction of all-trans retinoid acid (ATRA)—a differentiating agent currently used in clinical settings—restores autophagy in these cells. ATRA-induced autophagy is involved in granulocytes differentiation through a mechanism that involves among others the degradation of the PML-RARα oncoprotein. Arsenic trioxide (ATO) is another anti-cancer agent that promotes autophagy-dependent clearance of promyelocytic leukemia retinoic acid receptor alpha gene (PML-RARα) in APL cells. Hence, enhancing autophagy may have therapeutic benefits in maturation-resistant APL cells. However, the role of autophagy in response to APL therapy is not so simple, because some autophagy ...
Molecular & Cellular Oncology, 2019
Medecine sciences : M/S, 2017
Autophagy is a self-cannibalism process essential for tissue homeostasis, which can be activated ... more Autophagy is a self-cannibalism process essential for tissue homeostasis, which can be activated following different environmental stressful conditions. In normal cells, autophagy could act as a brake to prevent tumorigenesis, but cancer cells are able to hijack this process to their own benefit, to promote tumor growth and/or tumor resistance to anti-cancer therapies. Scientists and clinicians attempt to modulate this process to improve therapies, using autophagy inhibitors or activators, some of them being tested currently in clinical trials against several types of tumors. Thus, it appears that autophagy is at the center of a showdown between cancer cells and anti-cancer therapies. In this review, we focus on the mechanisms by which autophagy could be either the yin or the yang of cancers.
Autophagy Networks in Inflammation, 2016
The homeostasis between the oxidant and antioxidant levels in cells is altered in several disease... more The homeostasis between the oxidant and antioxidant levels in cells is altered in several diseases including cancer, neurodegenerative diseases, and inflammatory disorders. Macroautophagy (hereafter referred to as autophagy) is a redox (reduction/oxidation)-sensitive process that results in degradation of cellular constituents such as proteins, lipids, and mitochondria through the lysosomal pathway. There is a complex and mutual relationship between pathways that control levels of reactive oxygen species (ROS) and autophagy. Autophagy is activated by various stimuli in cells and ROS are one of these autophagy inducers. The accumulation of ROS induces autophagy both by direct effect on the core autophagy machinery and by indirect influence on the components of the autophagy-regulatory signaling pathway. In turn, autophagy regulates the abundance of ROS in cells by promoting the clearance of damaged mitochondria and oxidized cellular substrates and by modulating activity of the detoxifying antioxidant systems. ROS are also involved in the initiation of inflammation, a process that required the secretion of several inflammatory mediators. Here, we will discuss the regulation of inflammatory responses by autophagy as a consequence of the interplay of autophagy and ROS signaling pathways.
Cellular Microbiology, 2016
Cytotoxicity of many plant and bacterial toxins requires their endocytosis and retrograde transpo... more Cytotoxicity of many plant and bacterial toxins requires their endocytosis and retrograde transport from endosomes to the endoplasmic reticulum. Using cell fractionation and immunoblotting procedures, we have assessed the fate and action of the plant toxin ricin in rat liver in vivo, focusing on endosome-associated events and induction of apoptosis. Injected ricin rapidly accumulated in endosomes as an intact A/B heterodimer (5-90 min) and was later (15-90 min) partially translocated to cytosol as A-and B-chains. Unlike cholera and diphtheria toxins, which also undergo endocytosis in liver, neither in cell-free endosomes loaded by ricin in vivo nor upon incubation with endosomal lysates did ricin undergo degradation in vitro. A time-dependent translocation of ricin across the endosomal membrane occurred in cell-free endosomes. Endosome-located thioredoxin reductase-1 was required for translocation as shown by its physical association with ricin chains and effects of its removal and inhibition. Ricin induced in vivo intrinsic apoptosis as judged by increased cytochrome c content, activation of caspase-9 and caspase-3, and enrichment of DNA fragments in cytosol. Furthermore, reduced ricin and ricin B-chain caused cytochrome c release from mitochondria in vivo and in vitro, suggesting that the interaction of ricin B-chain with mitochondria is involved in ricin-induced apoptosis.
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, 2016
Autophagy (a Greek term meaning self-digestion) and apoptosis (a Greek term meaning “falling off”... more Autophagy (a Greek term meaning self-digestion) and apoptosis (a Greek term meaning “falling off”) constitute two distinct evolutionarily conserved processes that are involved in tissue homeostasis in metazoans. Dysfunction of one of both processes can result in development of human pathologies including cancer, neurodegenerative diseases, or inflammatory-related diseases. Autophagy and apoptosis share several signaling pathways and can mutually regulate each other to ensure cellular homeostasis in response to a given stress signal. Although autophagy has been often considered as a survival mechanism, a body of evidence reveals that autophagy can contribute to both caspase-dependent and caspase-independent programmed cell death. In this chapter, we summarize our current understanding of the molecular interplay between autophagy and death receptor signaling pathways and discuss how autophagy and autophagy-regulatory proteins can control receptor-mediated cell death signaling.
Biochemical Journal, 1994
The effects of u.v. A radiations on phospholipid synthesis were studied in the N.C.T.C. 2544 huma... more The effects of u.v. A radiations on phospholipid synthesis were studied in the N.C.T.C. 2544 human keratinocyte cell line, by using [14C]arachidonic acid, [14C]oleic acid or sodium [32P]orthophosphate as precursors. Cells were irradiated in Hanks' medium with 365 nm light at doses up to 19 J/cm2, and then phospholipid synthesis from the three precursors was studied. Under these conditions, only small alterations in the incorporation pattern of [14C]arachidonic into phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI)] were observed, for u.v. A irradiation doses up to 19 J/cm2. In contrast, with [14C]oleic acid as precursor, two additional spots were observed, which co-migrate with pure phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG) standards. The incorporation of [14C]oleic acid into PG and DPG was decreased in a dose-dependent manner after u.v. A exposure, with about 50% and 75% decreases at 9.5 J/cm2 and 19 J/cm2 resp...
Autophagy, 2015
activated protein kinase 8; MAP1LC3, microtubule-associated protein 1 light chain 3; MTOR, mechan... more activated protein kinase 8; MAP1LC3, microtubule-associated protein 1 light chain 3; MTOR, mechanistic target of rapamycin; MTORC1, mechanistic target of rapamycin complex 1; MTORC2, mechanistic target of rapamycin complex 2; NADPH, nicotinamide adenine dinucleotide phosphate; SQSTM1/p62, sequestosome 1; EGLN/PHD, egl-9 family hypoxia-inducible factor; RB1CC1/FIP200, RB1-inducible coiled-coil 1; RRAG, Ras-related GTP binding; RHEB, RAS homolog enriched in brain; ROS, reactive oxygen species; SLC1A5, solute carrier family 1 (neutral amino acid transporter) member 5; SLC7A5, solute carrier family 7 (amino acid transporter light chain, L system), member 5; SLC3A2, solute carrier family 3 (amino acid transporter heavy chain), member 2; TCA, tricarboxyic acid; TFEB, transcription factor EB; TSC, tuberous sclerosis; ULK1/2, unc-51 like autophagy activating kinase 1/2. The remarkable metabolic differences between cancer cells and normal cells result in the potential for targeted cancer therapy. The upregulation of glutaminolysis provides energetic advantages to cancer cells. The recently described link between glutaminolysis and autophagy, mediated by MTORC1, may constitute an attractive target for therapeutic strategies. A combination of therapies targeting simultaneously cell signaling, cancer metabolism, and autophagy can solve therapy resistance and tumor relapse problems, commonly observed in patients treated with most of the current targeted therapies. In this review we summarize the mechanistic link between glutaminolysis and autophagy, and discuss the impacts of these processes on cancer progression and the potential for therapeutic intervention.
American journal of cancer research, 2011
Tight regulation of both the NF-κB pathway and the autophagy process is necessary for maintenance... more Tight regulation of both the NF-κB pathway and the autophagy process is necessary for maintenance of cellular homeostasis. Deregulation of both pathways is frequently observed in cancer cells and is associated with tumorigenesis and tumor cell resistance to cancer therapies. Autophagy is involved in several cellular functions regulated by NF-κB including cell survival, differentiation, senescence, inflammation, and immunity. On a molecular level, autophagy and NF-κB share common upstream signals and regulators and can control each other through positive or negative feedback loops, thus ensuring homeostatic responses. Here, we summarize and discuss the most recent discoveries that shed new light on the complex interplay between autophagy and NF-κB signaling pathways; this certainly has functional relevance in tumorigenesis and tumor responses to therapy.
Cancer Drug Discovery and Development
... J Cell Sci 2006; 119:259–270. 52. Møller MT, Samari HR, Holden L, Seglen PO. Regulation of ma... more ... J Cell Sci 2006; 119:259–270. 52. Møller MT, Samari HR, Holden L, Seglen PO. Regulation of mammalian autophagy by protein phosphorylation. In: Klionsky DJ, ed. Autophagy. Georgetown, TX: Landes Bioscience 2004; 49–59. 53. ...
Autophagy, 2006
The downregulation of macroautophagy observed in cancer cells is associated with tumor progressio... more The downregulation of macroautophagy observed in cancer cells is associated with tumor progression. The regulation of macroautophagy by signaling pathways overlaps with the control of cell growth, proliferation, cell survival and death. Several tumor suppressor genes (PTEN, TSC2 and p53) involved in the mTOR signaling network have been shown to stimulate autophagy. In contrast, the oncoproteins involved in this network have the opposite effect. These findings, together with the discovery that haploinsufficiency of the tumor suppressor beclin 1 promotes tumorigenesis in various tissues in transgenic mice, give credibility to the idea that autophagy is a tumor suppressor mechanism. The induction of macroautophagy by cancer treatments may also contribute to cell eradication. However, cancer cells sometimes mobilize autophagic capacities in response to various stimuli without a fatal outcome, suggesting that they can also exploit macroautophagy for their own benefit.