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32 results on '"Porporato, Paolo Ettore"'

1. RICTOR/mTORC2 downregulation in BRAFV600E melanoma cells promotes resistance to BRAF/MEK inhibition

Author

Ponzone, Luca, Audrito, Valentina, Landi, Claudia, Moiso, Enrico, Levra Levron, Chiara, Ferrua, Sara, Savino, Aurora, Vitale, Nicoletta, Gasparrini, Massimiliano, Avalle, Lidia, Vantaggiato, Lorenza, Shaba, Enxhi, Tassone, Beatrice, Saoncella, Stefania, Orso, Francesca, Viavattene, Daniele, Marina, Eleonora, Fiorilla, Irene, Burrone, Giulia, Abili, Youssef, Altruda, Fiorella, Bini, Luca, Deaglio, Silvia, Defilippi, Paola, Menga, Alessio, Poli, Valeria, Porporato, Paolo Ettore, Provero, Paolo, Raffaelli, Nadia, Riganti, Chiara, Taverna, Daniela, Cavallo, Federica, and Calautti, Enzo

Published
2024
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4. The heme synthesis-export system regulates the tricarboxylic acid cycle flux and oxidative phosphorylation

Author

Fiorito, Veronica, Allocco, Anna Lucia, Petrillo, Sara, Gazzano, Elena, Torretta, Simone, Marchi, Saverio, Destefanis, Francesca, Pacelli, Consiglia, Audrito, Valentina, Provero, Paolo, Medico, Enzo, Chiabrando, Deborah, Porporato, Paolo Ettore, Cancelliere, Carlotta, Bardelli, Alberto, Trusolino, Livio, Capitanio, Nazzareno, Deaglio, Silvia, Altruda, Fiorella, Pinton, Paolo, Cardaci, Simone, Riganti, Chiara, and Tolosano, Emanuela

Published
2021
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5. Flvcr1a deficiency promotes heme-based energy metabolism dysfunction in skeletal muscle

Author

Mistretta, Miriam, primary, Fiorito, Veronica, additional, Allocco, Anna Lucia, additional, Ammirata, Giorgia, additional, Hsu, Myriam Y., additional, Digiovanni, Sabrina, additional, Belicchi, Marzia, additional, Napoli, Laura, additional, Ripolone, Michela, additional, Trombetta, Elena, additional, Mauri, PierLuigi, additional, Farini, Andrea, additional, Meregalli, Mirella, additional, Villa, Chiara, additional, Porporato, Paolo Ettore, additional, Miniscalco, Barbara, additional, Crich, Simonetta Geninatti, additional, Riganti, Chiara, additional, Torrente, Yvan, additional, and Tolosano, Emanuela, additional

Published
2024
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8. IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection

Author

Griffante, Gloria, primary, Hewelt-Belka, Weronika, additional, Albano, Camilla, additional, Gugliesi, Francesca, additional, Pasquero, Selina, additional, Castillo Pacheco, Sergio Fernando, additional, Bajetto, Greta, additional, Porporato, Paolo Ettore, additional, Mina, Erica, additional, Vallino, Marta, additional, Krapp, Christian, additional, Jakobsen, Martin Roelsgaard, additional, Purdy, John, additional, von Einem, Jens, additional, Landolfo, Santo, additional, Dell’Oste, Valentina, additional, and Biolatti, Matteo, additional

Published
2022
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9. Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer

Author

De Santis, Maria Chiara, primary, Gozzelino, Luca, additional, Margaria, Jean Piero, additional, Costamagna, Andrea, additional, Ratto, Edoardo, additional, Gulluni, Federico, additional, Di Gregorio, Enza, additional, Mina, Erica, additional, Lorito, Nicla, additional, Bacci, Marina, additional, Lattanzio, Rossano, additional, Sala, Gianluca, additional, Cappello, Paola, additional, Novelli, Francesco, additional, Giovannetti, Elisa, additional, Vicentini, Caterina, additional, Andreani, Silvia, additional, Delfino, Pietro, additional, Corbo, Vincenzo, additional, Scarpa, Aldo, additional, Porporato, Paolo Ettore, additional, Morandi, Andrea, additional, Hirsch, Emilio, additional, and Martini, Miriam, additional

Published
2022
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10. IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection [*Valentina Dell'Oste, *Matteo Biolatti, co-corresponding authors]

Author

Gloria, Griffante, Weronika, Hewelt-Belka, Albano, Camilla, Gugliesi, Francesca, Pasquero, Selina, Sergio Fernando Castillo Pacheco, Bajetto, Greta, Porporato, Paolo Ettore, Mina, Erica, Vallino, Marta, Christian, Krapp, Martin Roelsgaard Jakobsen, John, Purdy, Jens von Einem, Landolfo, Santo Giuseppe, Dell'Oste, Valentina, and Biolatti, Matteo

Subjects
glucose and lipid metabolism, human cytomegalovirus, lipidomics, IFI16, IFI16, glucose and lipid metabolism, human cytomegalovirus, lipidomics, virus-host interactions, virus-host interactions
Published
2022

11. IFI16 IMPACTS METABOLIC REPROGRAMMING DURING HUMAN CYTOMEGALOVIRUS INFECTION

Author

Griffante, Gloria, Weronika, Hewelt-Belka, Albano, Camilla, Gugliesi, Francesca, Pasquero, Selina, Bajetto, Greta, Porporato, Paolo Ettore, Mina, Erica, Vallino, Marta, Martin, Jakobsen, John, Purdy, Jens von Einem, Landolfo, Santo Giuseppe, Biolatti, Matteo, and Dell'Oste, Valentina

Published
2022

12. Phosphoinositide Conversion Inactivates R‐RAS and Drives Metastases in Breast Cancer

Author

Li, Huayi, primary, Prever, Lorenzo, additional, Hsu, Myriam Y., additional, Lo, Wen‐Ting, additional, Margaria, Jean Piero, additional, De Santis, Maria Chiara, additional, Zanini, Cristina, additional, Forni, Marco, additional, Novelli, Francesco, additional, Pece, Salvatore, additional, Di Fiore, Pier Paolo, additional, Porporato, Paolo Ettore, additional, Martini, Miriam, additional, Belabed, Hassane, additional, Nazare, Marc, additional, Haucke, Volker, additional, Gulluni, Federico, additional, and Hirsch, Emilio, additional

Published
2022
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14. Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer

Author

De Santis, Maria Chiara, Gozzelino, Luca, Margaria, Jean Piero, Costamagna, Andrea, Ratto, Edoardo, Gulluni, Federico, Di Gregorio, Enza, Mina, Erica, Lorito, Nicla, Bacci, Marina, Lattanzio, Rossano, Sala, Gianluca, Cappello, Paola, Novelli, Francesco, Giovannetti, Elisa, Vicentini, Caterina, Andreani, Silvia, Delfino, Pietro, Corbo, Vincenzo, Scarpa, Aldo, Porporato, Paolo Ettore, Morandi, Andrea, Hirsch, Emilio, and Martini, Miriam

Abstract

ObjectivePancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited therapeutic options. However, metabolic adaptation to the harsh PDAC environment can expose liabilities useful for therapy. Targeting the key metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) and its downstream pathway shows efficacy only in subsets of patients but gene modifiers maximising response remain to be identified.DesignThree independent cohorts of PDAC patients were studied to correlate PI3K-C2γ protein abundance with disease outcome. Mechanisms were then studied in mouse (KPC mice) and cellular models of PDAC, in presence or absence of PI3K-C2γ (WT or KO). PI3K-C2γ-dependent metabolic rewiring and its impact on mTORC1 regulation were assessed in conditions of limiting glutamine availability. Finally, effects of a combination therapy targeting mTORC1 and glutamine metabolism were studied in WT and KO PDAC cells and preclinical models.ResultsPI3K-C2γ expression was reduced in about 30% of PDAC cases and was associated with an aggressive phenotype. Similarly, loss of PI3K-C2γ in KPC mice enhanced tumour development and progression. The increased aggressiveness of tumours lacking PI3K-C2γ correlated with hyperactivation of mTORC1 pathway and glutamine metabolism rewiring to support lipid synthesis. PI3K-C2γ-KO tumours failed to adapt to metabolic stress induced by glutamine depletion, resulting in cell death.ConclusionLoss of PI3K-C2γ prevents mTOR inactivation and triggers tumour vulnerability to RAD001 (mTOR inhibitor) and BPTES/CB-839 (glutaminase inhibitors). Therefore, these results might open the way to personalised treatments in PDAC with PI3K-C2γ loss.

Published
2023
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15. Investigation of the apelin adipokine as a potential therapeutic target for breast cancer patients in the context of obesity

Author

UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - Faculté de pharmacie et des sciences biomédicales, Sonveaux, Pierre, Knauf, Claude, Porporato, Paolo Ettore, Gallez, Bernard, Brichard, Sonia, Jordan, Bénédicte, Cani, Patrice, Gourgue, Florian, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - Faculté de pharmacie et des sciences biomédicales, Sonveaux, Pierre, Knauf, Claude, Porporato, Paolo Ettore, Gallez, Bernard, Brichard, Sonia, Jordan, Bénédicte, Cani, Patrice, and Gourgue, Florian

Abstract

Obesity is known to increase the risk of developing breast cancer, to promote mammary tumor progression and to reduce the response to chemotherapy. However, the mechanisms involved in the association between obesity and breast cancer are still not well understood. As the apelin adipokine is overexpressed in obesity, our project was designed to investigate the potential effects of apelin on breast cancer progression in the context of obesity. We showed in mice that reproducing obesity-relevant levels of apelin in lean mice promoted breast cancer growth and metastatization. In addition, the administration of an apelinergic antagonist in obese mice succeeded in reducing breast cancer progression. Finally, we showed in human breast cancer patients that high tumoral apelin expression was associated with a reduced response to neoadjuvant chemotherapy. These results highlighted that targeting the apelinergic system could be beneficial for obese breast cancer patients., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2020

Published
2020

18. Mitochondrial metabolism and cancer

Author

Porporato, Paolo Ettore, primary, Filigheddu, Nicoletta, additional, Pedro, José Manuel Bravo-San, additional, Kroemer, Guido, additional, and Galluzzi, Lorenzo, additional

Published
2017
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19. Flvcr1adeficiency promotes heme-based energy metabolism dysfunction in skeletal muscle

Author

Mistretta, Miriam, Fiorito, Veronica, Allocco, Anna Lucia, Ammirata, Giorgia, Hsu, Myriam Y., Digiovanni, Sabrina, Belicchi, Marzia, Napoli, Laura, Ripolone, Michela, Trombetta, Elena, Mauri, PierLuigi, Farini, Andrea, Meregalli, Mirella, Villa, Chiara, Porporato, Paolo Ettore, Miniscalco, Barbara, Crich, Simonetta Geninatti, Riganti, Chiara, Torrente, Yvan, and Tolosano, Emanuela

Abstract

The definition of cell metabolic profile is essential to ensure skeletal muscle fiber heterogeneity and to achieve a proper equilibrium between the self-renewal and commitment of satellite stem cells. Heme sustains several biological functions, including processes profoundly implicated with cell metabolism. The skeletal muscle is a significant heme-producing body compartment, but the consequences of impaired heme homeostasis on this tissue have been poorly investigated. Here, we generate a skeletal-muscle-specific feline leukemia virus subgroup C receptor 1a (FLVCR1a) knockout mouse model and show that, by sustaining heme synthesis, FLVCR1a contributes to determine the energy phenotype in skeletal muscle cells and to modulate satellite cell differentiation and muscle regeneration.

Published
2024
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24. The Diacylglycerol Kinase α/Atypical PKC/β1 Integrin Pathway in SDF-1α Mammary Carcinoma Invasiveness

Author

Rainero, Elena, primary, Cianflone, Cristina, additional, Porporato, Paolo Ettore, additional, Chianale, Federica, additional, Malacarne, Valeria, additional, Bettio, Valentina, additional, Ruffo, Elisa, additional, Ferrara, Michele, additional, Benecchia, Fabio, additional, Capello, Daniela, additional, Paster, Wolfgang, additional, Locatelli, Irene, additional, Bertoni, Alessandra, additional, Filigheddu, Nicoletta, additional, Sinigaglia, Fabiola, additional, Norman, Jim C., additional, Baldanzi, Gianluca, additional, and Graziani, Andrea, additional

Published
2014
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26. Assessment of melanoma extent and melanoma metastases invasion using electron paramagnetic resonance and bioluminescence imaging

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de médecine nucléaire, Godechal, Quentin, Defresne, Florence, Danhier, Pierre, Levêque, Philippe, Porporato, Paolo Ettore, Sonveaux, Pierre, Baurain, Jean-François, Feron, Olivier, Gallez, Bernard, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de médecine nucléaire, Godechal, Quentin, Defresne, Florence, Danhier, Pierre, Levêque, Philippe, Porporato, Paolo Ettore, Sonveaux, Pierre, Baurain, Jean-François, Feron, Olivier, and Gallez, Bernard

Abstract

The clinical outcome of melanoma depends on the local and distant spread of the disease at the time of diagnosis, as the estimated 5-year survival rate is about 100% for superficial melanoma diagnosed early, but less than 10% for melanoma that has disseminated to major organs such as lungs. There is a crucial need for new effective methods for the detection and the characterization of melanomas. In the pre-clinical setting, this will help to understand the factors that contribute to the malignancy while the transfer into the clinic will contribute to an early effective treatment of patients. Melanoma lesions can be detected by electron paramagnetic resonance (EPR) using paramagnetic properties of melanin pigments. As part of the development of EPR imaging to characterize melanomas, we evaluated in the present study the usefulness of EPR to report on the extension of lung metastases by comparing the method with bioluminescence imaging using B16 melanoma cells expressing luciferase. B16 melanoma cells were injected subcutaneously or intravenously in C57/BL6 mice. The primary tumors or the lung colonization by melanoma cells was measured after several delay periods to obtain several degrees of invasiveness. The animals were measured in-vivo with bioluminescence after i.v. injection of luciferin. The primary tumors or lungs were then excised. After freeze-drying, the content of melanin in lungs was measured and imaged by EPR at 9 GHz. We observed a direct relationship between the EPR intensity and the bioluminescence intensity. Another tumor model (KHT sarcoma), non-pigmented but expressing luciferase, was used to confirm that the EPR signal was directly linked to the melanin pigment present in the tumors. Copyright © 2011 John Wiley & Sons, Ltd.

Published
2011

27. Mitochondrial metabolism and cancer

Author

Porporato, Paolo Ettore, Filigheddu, Nicoletta, Pedro, José Manuel Bravo-San, Kroemer, Guido, and Galluzzi, Lorenzo

Abstract

Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view has been instrumental for the development of powerful imaging tools that are still used in the clinics, it is now clear that mitochondria play a key role in oncogenesis. Besides exerting central bioenergetic functions, mitochondria provide indeed building blocks for tumor anabolism, control redox and calcium homeostasis, participate in transcriptional regulation, and govern cell death. Thus, mitochondria constitute promising targets for the development of novel anticancer agents. However, tumors arise, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system, and many immunological functions rely on intact mitochondrial metabolism. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial metabolism for cancer therapy.

Published
2018
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29. Metabolic Aspects of Anthracycline Cardiotoxicity

Author

Angela Della Sala, Carlo G. Tocchetti, Paolo E. Porporato, Alessandra Ghigo, Michele Russo, Russo, Michele, Della Sala, Angela, Tocchetti, Carlo Gabriele, Porporato, Paolo Ettore, and Ghigo, Alessandra

Subjects
0301 basic medicine, Anthracycline, Cell Survival, Iron, medicine.medical_treatment, Cardiomyopathy, Antineoplastic Agents, 030204 cardiovascular system & hematology, Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Autophagy, medicine, Humans, Anthracyclines, Myocytes, Cardiac, Pharmacology (medical), Doxorubicin, Cardiotoxicity, Chemotherapy, Cardio-oncology (MG Fradley, Section Editor), business.industry, Myocardium, Fatty Acids, medicine.disease, Cardiotoxicity, Cardiac metabolism, Doxorubicin, Review article, 030104 developmental biology, Oncology, Heart failure, Disease Susceptibility, Dexrazoxane, Insulin Resistance, business, Glycolysis, Oxidation-Reduction, Cardiac metabolism, Biomarkers, medicine.drug
Abstract

Opinion statementHeart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. At the molecular level, cardiac side effects of DOXO have been associated to mitochondrial dysfunction, DNA damage, impairment of iron metabolism, apoptosis, and autophagy dysregulation. On these bases, the antioxidant and iron chelator molecule, dexrazoxane, currently represents the unique FDA-approved cardioprotectant for patients treated with anthracyclines.A less explored area of research concerns the impact of DOXO on cardiac metabolism. Recent metabolomic studies highlight the possibility that cardiac metabolic alterations may critically contribute to the development of DOXO cardiotoxicity. Among these, the impairment of oxidative phosphorylation and the persistent activation of glycolysis, which are commonly observed in response to DOXO treatment, may undermine the ability of cardiomyocytes to meet the energy demand, eventually leading to energetic failure. Moreover, increasing evidence links DOXO cardiotoxicity to imbalanced insulin signaling and to cardiac insulin resistance. Although anti-diabetic drugs, such as empagliflozin and metformin, have shown interesting cardioprotective effects in vitro and in vivo in different models of heart failure, their mechanism of action is unclear, and their use for the treatment of DOXO cardiotoxicity is still unexplored.This review article aims at summarizing current evidence of the metabolic derangements induced by DOXO and at providing speculations on how key players of cardiac metabolism could be pharmacologically targeted to prevent or cure DOXO cardiomyopathy.

Published
2021

30. The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

Author

Elena Rainero, Nicoletta Filigheddu, Cristina Cianflone, Valeria Malacarne, Gianluca Baldanzi, Jim C. Norman, Irene Locatelli, Fabiola Sinigaglia, Wolfgang Paster, Daniela Capello, Fabio Benecchia, Valentina Bettio, Federica Chianale, Alessandra Bertoni, Andrea Graziani, Elisa Ruffo, Paolo E. Porporato, Michele Ferrara, Rainero, Elena, Cianflone, Cristina, Porporato, Paolo Ettore, Chianale, Federica, Malacarne, Valeria, Bettio, Valentina, Ruffo, Elisa, Ferrara, Michele, Benecchia, Fabio, Capello, Daniela, Paster, Wolfgang, Locatelli, Irene, Bertoni, Alessandra, Filigheddu, Nicoletta, Sinigaglia, Fabiola, Norman, Jim C., Baldanzi, Gianluca, Graziani, Andrea, and UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique

Subjects
Genetics and Molecular Biology (all), Cell signaling, Signal transduction, Biochemistry, Epithelium, Metastasis, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Molecular Cell Biology, Basic Cancer Research, Medicine and Health Sciences, Pseudopodia, Cytoskeleton, Second Messenger System, Protein Kinase C, Multidisciplinary, Integrin beta1, Medicine (all), Mechanisms of Signal Transduction, Cell migration, Lipids, Signaling Cascades, Cell biology, rac GTP-Binding Proteins, Rac GTP-Binding Proteins, Protein Transport, Oncology, Matrix Metalloproteinase 9, Medicine, Female, Anatomy, Cellular Structures and Organelles, Breast Neoplasm, Research Article, Human, Signal Transduction, Diacylglycerol Kinase, Science, Integrin, Lipid signaling, Breast Neoplasms, Phosphoinositide Signal Transduction, Biology, Oncogenic signaling, Lipid Mediators, Cell Line, Tumor, Humans, Neoplasm Invasiveness, rac GTP-Binding Protein, Protein kinase C, Diacylglycerol kinase, Neoplasm Invasivene, Biology and life sciences, Antigens, CD29, Epithelial Cells, Protein kinase C signaling, Chemokine CXCL12, Biological Tissue, Cell movement signaling, Phospholipid Signaling Cascade, biology.protein
Abstract

Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells. © 2014 Rainero et al.

Published
2014
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31. Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis.

Author

Dhup S, Dadhich RK, Porporato PE, and Sonveaux P

Subjects
Humans, Neoplasm Invasiveness, Lactic Acid metabolism, Neoplasm Metastasis physiopathology, Neoplasms blood supply, Neoplasms metabolism, Neovascularization, Pathologic metabolism
Abstract

High rate of glycolysis is a metabolic hallmark of cancer. While anaerobic glycolysis promotes energy production under hypoxia, aerobic glycolysis, the Warburg effect, offers a proliferative advantage through redirecting carbohydrate fluxes from energy production to biosynthetic pathways. To fulfill tumor cell needs, the glycolytic switch is associated with elevated glucose uptake and lactic acid release. Altered glucose metabolism is the basis of positron emission tomography using the glucose analogue tracer [18F]- fluorodeoxyglucose, a widely used clinical application for tumor diagnosis and monitoring. On the other hand, high levels of lactate have been associated with poor clinical outcome in several types of human cancers. Although lactic acid was initially considered merely as an indicator of the glycolytic flux, many evidences originally from the study of normal tissue physiology and more recently transposed to the tumor situation indicate that lactic acid, i.e. the lactate anion and protons, directly contributes to tumor growth and progression. Here, we briefly review the current knowledge pertaining to lactic acidosis and metastasis, lactate shuttles, the influence of lactate on redox homeostasis, lactate signaling and lactate-induced angiogenesis in the cancer context. The monocarboxylate transporters MCT1 and MCT4 have now been confirmed as prominent facilitators of lactate exchanges between cancer cells with different metabolic behaviors and between cancer and stromal cells. We therefore address the function and regulation of MCTs, highlighting MCT1 as a novel anticancer target. MCT1 inhibition allows to simultaneously disrupt metabolic cooperativity and angiogenesis in cancer with a same agent, opening a new path for novel anticancer therapies.

Published
2012
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32. Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells.

Author

Filigheddu N, Cutrupi S, Porporato PE, Riboni F, Baldanzi G, Chianale F, Fortina E, Piantanida P, De Bortoli M, Vacca G, Graziani A, and Surico N

Subjects
Cell Culture Techniques, Cell Line, Tumor, Cell Movement, Diacylglycerol Kinase analysis, Humans, Neoplasm Invasiveness, Receptors, Estrogen analysis, Receptors, Estrogen metabolism, Breast Neoplasms enzymology, Breast Neoplasms pathology, Diacylglycerol Kinase metabolism, Hepatocyte Growth Factor pharmacology
Abstract

Background: Estrogen receptor (ER)-negative breast cancers have a worse prognosis than ER-positive cancers, being more aggressive and overexposed to stimuli leading to their progression. Hepatocyte growth factor (HGF) has been associated with proliferation, migration and invasion of tumor cells, and several tumors, including those of breast cancer, produce HGF and overexpress its receptor. Diacylglycerol kinases (Dgks), which phosphorylate diacylglycerol to phosphatidic acid, are key regulators of cell signaling. Our research was focused on their role in HGF-induced invasion of MDA-MB-231 cells, a model of ER-negative breast cancer., Materials and Methods: Dgk activity was evaluated with a kinase assay, MDA-MB-231 cell invasion via culturing of cells in matrigel-coated transwells, and anchorage-independent growth was assessed using a soft agar assay., Results: HGF induces Dgk activation in MDA-MB-231 cells that is required for cell invasiveness. Moreover, Dgks are involved in MDA-MB-231 anchorage-independent growth., Conclusion: Dgks could be a target for ER-negative breast cancer therapy.

Published
2007

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