16 results on '"Martínez-Díez, Marta"'
Search Results
2. PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin
- Author
-
Lucena-Agell, Daniel, primary, Guillén, María José, additional, Matesanz, Ruth, additional, Álvarez-Bernad, Beatriz, additional, Hortigüela, Rafael, additional, Avilés, Pablo, additional, Martínez-Díez, Marta, additional, Santamaría-Núñez, Gema, additional, Contreras, Julia, additional, Plaza-Menacho, Iván, additional, Giménez-Abián, Juan F., additional, Oliva, María A., additional, Cuevas, Carmen, additional, and Díaz, J. Fernando, additional
- Published
- 2024
- Full Text
- View/download PDF
3. Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival
- Author
-
Losada, Alejandro, Muñoz-Alonso, María José, Martínez-Díez, Marta, Gago, Federico, Domínguez, Juan Manuel, Martínez-Leal, Juan Fernando, and Galmarini, Carlos M.
- Published
- 2018
- Full Text
- View/download PDF
4. Antitumoral Effect of Plocabulin in High Grade Serous Ovarian Carcinoma Cell Line Models
- Author
-
Heredia-Soto, Victoria, primary, Escudero, Javier, additional, Miguel, María, additional, Ruiz, Patricia, additional, Gallego, Alejandro, additional, Berjón, Alberto, additional, Hernández, Alicia, additional, Martínez-Díez, Marta, additional, Zheng, Shuyu, additional, Tang, Jing, additional, Hardisson, David, additional, Feliu, Jaime, additional, Redondo, Andrés, additional, and Mendiola, Marta, additional
- Published
- 2022
- Full Text
- View/download PDF
5. PM060184, a new tubulin binding agent with potent antitumor activity including P-glycoprotein over-expressing tumors
- Author
-
Martínez-Díez, Marta, Guillén-Navarro, María José, Pera, Benet, Bouchet, Benjamin Pierre, Martínez-Leal, Juan Fernando, Barasoain, Isabel, Cuevas, Carmen, Andreu, Jose M., García-Fernández, Luis Francisco, Díaz, Fernando J., Avilés, Pablo, and Galmarini, Carlos M.
- Published
- 2014
- Full Text
- View/download PDF
6. Evaluación del marcador HE4, CA125 e Índice ROMA en el diagnóstico diferencial de las masas anexiales
- Author
-
Martínez Díez, Marta, Condor-Muñoz, Luis Miguel, Gonzalez-Mesa, Ernesto Santiago, Cirugía, Obstetricia y Ginecología, Cóndor Muñoz, Luis, and González Mesa, Ernesto
- Subjects
CA125 ,Masas anexiales ,Cáncer de ovario ,HE4 ,Índice ROMA ,Aparato genital femenino -- Cáncer ,Tesis Doctoral - Abstract
Las masas anexiales son un hallazgo común en la práctica ginecológica, y a menudo se presentan dilemas tanto en el diagnóstico como en su manejo. El fin último del manejo de las mismas es el diagnóstico precoz del cáncer de ovario, el cual presenta una supervivencia baja en estadios avanzados y frente al cual todavía no existe métodos de screening. En la actualidad, el CA125 es el marcador tumoral recomendado tanto en la Oncoguía SEGO del Cáncer Epitelial de Ovario 2014 como en las guías NCCN 2015 para establecer un diagnóstico frente a una masa anexial sospechosa o como ayuda en la detección de carcinoma ovárico residual en pacientes que han recibido quimioterapia de primera línea. Sin embargo, no es recomendado como método de detección precoz en pacientes asintomáticas, dada su falta de sensibilidad para el diagnóstico de cánceres de ovario en estadio I, así como su falta de especificidad. Hipótesis principales 1. El marcador tumoral HE4, aplicado a las pacientes de nuestro medio, presenta una capacidad diagnóstica mayor al CA125 en el diagnóstico diferencial de las masas ováricas, principalmente en pacientes premenopáusicas. 2. El Índice ROMA tiene una mayor capacidad diagnóstica que los marcadores HE4 y CA125 considerados aisladamente para la valoración de las tumoraciones ováricas en pacientes posmenopáusicas. 3. El Índice ROMA y HE4 poseen una mejor capacidad diagnóstica que el Risk of Malignancy Index (RMI) en el diagnóstico diferencial de masas anexiales. Material y Método Estudio prospectivo, de tipo observacional, de una muestra de 96 pacientes intervenidas quirúrgicamente por masas o quistes anexiales sospechosos en el Hospital Materno Infantil de Málaga, Hospital Comarcal de Antequera y Hospital Comarcal de la Axarquía, a las cuales se les determinó los marcadores tumorales CA125, HE4, CA19.9, y los Índices de Riesgo ROMA y Risk of Malignancy Index (RMI), con objeto de valorar el nuevo marcador HE4 y el Índice ROMA frente al marcador existente (CA125). Para la realización del estudio se ha tomado como muestra aquellas pacientes derivadas a cirugía por masas o quistes anexiales desde Enero de 2014 hasta agosto de 2015, que cumplieran con unos criterios de inclusión y exclusión, por la necesidad de un resultado histopatológico que permitiera comparar el diagnóstico de sospecha con un diagnóstico definitivo y poder evaluar los marcadores CA125 y HE4, el Índice ROMA y el RMI. Resultados Un total de 96 pacientes fueron derivadas a cirugía por masas o quistes anexiales, siendo diagnosticadas 40 pacientes (41.7%) de una patología benigna, 40 pacientes (41.7%) de un tumor maligno de ovario, 6 pacientes (6.25%) de tumor ovárico borderline y 10 (10.4%) de un tumor metastásico. En cuanto a los tumores malignos de ovario, 22 fueron serosos, 2 mucinosos, 3 endometrioides, 10 de células claras, 2 mixtos epiteliales y mesenquimales y un tumor germinal. La sensibilidad del marcador CA125 fue mayor (97.5%), que la sensibilidad del marcador HE4 y que la del Índice ROMA (90% y 95%, respectivamente). Sin embargo, el marcador HE4 demostró la mayor especificidad, con un 87.5%, frente al 62.5 % y 77.5% del CA125 e Índice ROMA. En el caso de las pacientes premenopáusicas, el AUC del marcador HE4 es claramente superior al del CA125 (AUCHE4 PRE= 0.960 [IC 0.909-1.000] vs AUCCA125 PRE= 0.823 [IC 0.705-0.942]). En las pacientes posmenopáusicas, sin embargo, el AUC mayor es el del Índice ROMA (AUC I.R POS= 0.896 [ IC 0.833-0.958]), seguido del AUC del marcador HE4 (AUCHE4 POS= 0.886 [IC 0.778-0.995]) , siendo el menor el AUC del marcador CA125 (AUCCA125 POS= 0.770 [IC 0.627-0.914]). Conclusiones Nuestros resultados muestran, en consonancia con lo publicado hasta ahora, que el marcador HE4 mejora la especificidad del CA125 a la hora de diferenciar entre patología benigna y maligna, presentando además una mejor capacidad diagnóstica en pacientes premenopáusicas que el CA125. El Índice ROMA posee mayor capacidad diagnóstica en pacientes posmenopáusicas. Tanto el marcador HE4 como el Índice ROMA, poseen una mejor capacidad diagnóstica que el Risk of Malignancy Index (RMI) para el diagnóstico diferencial de masas anexiales, según se desprende de los valores de AUC obtenidos, por lo que de acuerdo con la evidencia disponible, podemos concluir que el marcador HE4 y el Índice ROMA superan al marcador CA125 en el diagnóstico diferencial de masas anexiales, siendo herramientas útiles en el diagnóstico del cáncer de ovario.
- Published
- 2016
7. PM060184, a new tubulin binding agent with potent antitumor activity including P-glycoprotein over-expressing tumors
- Author
-
Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Consejo Superior de Investigaciones Científicas (España), Martínez-Díez, Marta, Guillén-Navarro, María José, Pera, Benet, Bouchet, Benjamin Pierre, Martínez-Leal, Juan Fernando, Barasoain, Isabel, Cuevas, Carmen, Andreu, José Manuel, García-Fernández, Luis F., Díaz, José Fernando, Avilés, Pablo, Galmarini, Carlos M., Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Consejo Superior de Investigaciones Científicas (España), Martínez-Díez, Marta, Guillén-Navarro, María José, Pera, Benet, Bouchet, Benjamin Pierre, Martínez-Leal, Juan Fernando, Barasoain, Isabel, Cuevas, Carmen, Andreu, José Manuel, García-Fernández, Luis F., Díaz, José Fernando, Avilés, Pablo, and Galmarini, Carlos M.
- Abstract
PM060184 belongs to a new family of tubulin-binding agents originally isolated from the marine sponge Lithoplocamia lithistoides. This compound is currently produced by total synthesis and is under evaluation in clinical studies in patients with advanced cancer diseases. It was recently published that PM060184 presents the highest known affinities among tubulin-binding agents, and that it targets tubulin dimers at a new binding site. Here, we show that PM060184 has a potent antitumor activity in a panel of different tumor xenograft models. Moreover, PM060184 is able to overcome P-gp mediated resistance in vivo, an effect that could be related to its high binding affinity for tubulin. To gain insight into the mechanism responsible of the observed antitumor activity, we have characterized its molecular and cellular effects. We have observed that PM060184 is an inhibitor of tubulin polymerization that reduces microtubule dynamicity in cells by 59%. Interestingly, PM060184 suppresses microtubule shortening and growing at a similar extent. This action affects cells in interphase and mitosis. In the first case, the compound induces a disorganization and fragmentation of the microtubule network and the inhibition of cell migration. In the second case, it induces the appearance of multipolar mitosis and lagging chromosomes at the metaphase plate. These effects correlate with prometaphase arrest and induction of caspase-dependent apoptosis or appearance of cells in a multinucleated interphase-like state unrelated to classical apoptosis pathways. Taken together, these results indicate that PM060184 represents a new tubulin binding agent with promising potential as an anticancer agent.
- Published
- 2014
8. Biogénesis de la mitocondria durante el ciclo celular y sus alteraciones en cáncer
- Author
-
Martínez-Díez, Marta, Cuezva Marcos, José Manuel, Universidad Autónoma de Madrid. Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa (CBM), and Cuezva, José M.
- Subjects
Cáncer - Tesis Doctorales ,Mitocondrias - Biogénesis - Tesis Doctorales ,Cáncer ,Mitocondrias - Abstract
Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de consulta: 29-02-2008, Mitochondria play essential roles in cellular energetic metabolism, the execution of cell death and intracellular calcium and reactive oxygen species signalling. A growing number of human diseases are nowadays associated with the molecular and/or functional alteration of mitochondria. The results reported in this thesis emphasize the role of the mitochondria in cancer biology. In this regard, Otto Warburg reported, as early as in 1924, that the glycolytic phenotype of tumors results from mitochondrial malfunction in the cancer cell. However, his hypothesis has been basically neglected until recently. Herein, we have studied in normal and tumor biopsies derived from the same patients the changes in the expression level of bioenergetic and structural mitochondrial proteins concurrently with the expression of glycolytic markers of the cell, the so-called “bioenergetic signature”. In agreement with previous findings in other carcinomas, the results obtained in squamous carcinomas of the oesophagus support the original Warburg hypothesis because we observed a reduction of the bioenergetic competence of the organelle when compared to normal oesophageal tissue. In contrast, in prostate adenocarcinomas we observed no alterations of the bioenergetic signature what might suggest that carcinogenesis affects the phenotype of mitochondria in a tissue-specific manner. The finding of an alteration in the metabolic proteome of cancer as a common feature of most type of carcinomas led us to consider the “bioenergetic signature” as a tool for the diagnosis and prognosis of cancer patients. Indeed, the use of these markers of metabolism allowed the molecular discrimination of melanomas from its metastasis as well as a group of melanoma patients with worse prognosis. Furthermore, the β-F1/GAPDH ratio provided a significant marker of disease progression for melanoma patients. From the mechanistic point of view, we have studied the effect of oncogenes (RAS, PDGF, AKT and EBV) on the “bioenergetic signature” and rates of cellular glycolysis. We find a variable effect of the different oncogenes in the energetic metabolism of the cell illustrating that tumor progression is linked to changes in the bioenergetic phenotype obtaining that tumor progression selects apparently cells with a higher glycolytic metabolism., Since it appears that alterations in mitochondrial physiology contribute to the Warburg effect, a question arises: which is the advantage and mechanistic contribution of the downregulation of oxidative phosphorylation for the cancer cell? In this regard, we show that the activity of the H+-ATP synthase participates in the execution of cell death by controlling the generation of reactive oxygen species which in turn promote a severe oxidative damage to mitochondrial proteins, favouring in this way the release of apoptogenic molecules from the organelle. These results provide an additional evidence linking metabolism to cell death and support strongly that the acquisition of a Warburg phenotype is another strategy of cancer cells in order ensure its perpetuation. Our knowledge of the basic cell biology and on the timing and mechanism that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. In this work we document the timing of the biosynthesis of different mitochondrial constituents during progression through the cell cycle and illustrate the relevance of the control of translation for appropriate biogenesis of mitochondria. In this regard, we show that the 3’UTR of β-mRNA controls the synthesis of the protein at G2/M, a stage when full development of the mitochondrial membrane potential is attained. Moreover, we document the dynamics and morphological changes experimented by mitochondria during mitosis. A long-standing dogma of cellular and evolutionary biology has been that H+-ATP synthases of F-type are exclusively present in the inner membrane of mitochondria of cell of mammals. However, recent reports claim that this complex is localised at the plasma membrane of human hepatocytes and tumor and endothelial cells. Here we show, using four different antibodies raised against the β-chain of the mitochondrial H+-ATP synthase, and various immunolocalitation techniques and subcellular fractionation experiments, that there is no molecular evidence that could support an ectopic expression of the β-chain on the cell-surface of these cells., Este trabajo ha sido realizado en el laboratorio del Doctor José Manuel Cuezva Marcos, Catedrático del Departamento de Biología Molecular del Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), de la Facultad de Ciencias de la Universidad Autónoma de Madrid (Octubre 2001-Septiembre 2005). Durante este periodo, la licenciada Marta Martínez Diez ha disfrutado de una Beca predoctoral del Fondo de Investigaciones Sanitarias del Ministerio de Sanidad y Consumo (Octubre 2001-Julio 2002), asociada al proyecto de investigación 01/380 y de una Beca Predoctoral de Formación de Personal Investigador del Ministerio de Ciencia y Tecnología (Julio 2002-Septiembre 2005), asociada al proyecto de investigación BMC2001-0710.
- Published
- 2008
9. Biogenesis and Dynamics of Mitochondria during the Cell Cycle: Significance of 39UTRs
- Author
-
Martínez-Díez, Marta, Santamaría, Gema, Ortega, Álvaro D., Cuezva, José M., Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Fundación Mutua Madrileña, and Fundación Ramón Areces
- Subjects
OXPHOS proteins ,Human cancer - Abstract
Article available at http://dx.doi.org/10.1371/journal.pone.0000107, Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of b-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (DYm) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of b-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 39UTR of the transcript. The 39UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated b-F1-ATPase expression in human cancer., M.M-D, G.S. and A.D.O are/were recipients of predoctoral fellowships from the Ministerio de Educación y Ciencia, Spain. This work was supported by grants from the Ministerio de Sanidad (PI041255), Educación y Ciencia (SAF-2005- 4001 and BMC2001-0710)and Fundación Mutua Madrileña, Spain. The CBMSO is the recipient of an institutional grant from Fundación Ramón Areces.
- Published
- 2006
10. Efficient execution of cell death in non-glycolytic cells requires the generation of ROS controlled by the activity of mitochondrial H+-ATP synthase
- Author
-
Santamaría, Gema, Martínez-Díez, Marta, Fabregat, Isabel, Cuezva, José M., Ministerio de Ciencia y Tecnología (España), Ministerio de Sanidad y Consumo (España), and Fundación Ramón Areces
- Subjects
H+-ATP synthase - Abstract
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version Carcinogenesis 2006 27(5):925-935 is available at: http://dx.doi.org/10.1093/carcin/bgi315, There is a large body of clinical data documenting that most human carcinomas contain reduced levels of the catalytic subunit of the mitochondrial H+-ATP synthase. In colon and lung cancer this alteration correlates with a poor patient prognosis. Furthermore, recent findings in colon cancer cells indicate that downregulation of the H+-ATP synthase is linked to the resistance of the cells to chemotherapy. However, the mechanism by which the H+-ATP synthase participates in cancer progression is unknown. In this work, we show that inhibitors of the H+-ATP synthase delay staurosporine (STS)-induced cell death in liver cells that are dependent on oxidative phosphorylation for energy provision whereas it has no effect on glycolytic cells. Efficient execution of cell death requires the generation of reactive oxygen species (ROS) controlled by the activity of the H+-ATP synthase in a process that is concurrent with the rapid disorganization of the cellular mitochondrial network. The generation of ROS after STS treatment is highly dependent on the mitochondrial membrane potential and most likely caused by reverse electron flow to Complex I. The generated ROS promote the carbonylation and covalent modification of cellular and mitochondrial proteins. Inhibition of the activity of the H+-ATP synthase blunted ROS production prevented the oxidation of cellular proteins and the modification of mitochondrial proteins delaying the release of cytochrome c and the execution of cell death. The results in this work establish the downregulation of the H+-ATP synthase, and thus of oxidative phosphorylation, as part of the molecular strategy adapted by cancer cells to avoid ROS-mediated cell death. Furthermore, the results provide a mechanistic explanation to understand chemotherapeutic resistance of cancer cells that rely on glycolysis as the main energy provision pathway., G.S. and M.M-D. were supported by pre-doctoral fellowships from the Ministerio de Ciencia y Tecnología. This work was supported by grants from the Ministerio de Sanidad y Consumo (PI041255), Comunidad de Madrid (SAL/0026/2004) and Ministerio de Ciencia y Tecnología (BMC2001-0710). The CBMSO receives an institutional grant from Fundación Ramón Areces.
- Published
- 2005
11. Overexpression of Akt converts radial growth melanoma to vertical growth melanoma
- Author
-
US Department of Veterans Affairs, National Institutes of Health (US), Jamie Rabinowitch Davis Foundation for Melanoma Research, Minsk Foundation, Ministerio de Ciencia y Tecnología (España), Dermatology Foundation, Govindarajan, Baskaran, Sligh, James E., Vincent, Bethaney J., Li, Meiling, Canter, Jeffrey A., Nickoloff, Brian J., Rodenburg, Richard J., Smeitink, Jan A., Oberley, Larry, Zhang, Yuping, Slingerland, Joyce, Arnold, Rebecca S., Lambeth, J. David, Cohen, Cynthia, Hilenski, Lu, Griendling, Kathy, Martínez-Díez, Marta, Cuezva, José M., Arbiser, Jack L., US Department of Veterans Affairs, National Institutes of Health (US), Jamie Rabinowitch Davis Foundation for Melanoma Research, Minsk Foundation, Ministerio de Ciencia y Tecnología (España), Dermatology Foundation, Govindarajan, Baskaran, Sligh, James E., Vincent, Bethaney J., Li, Meiling, Canter, Jeffrey A., Nickoloff, Brian J., Rodenburg, Richard J., Smeitink, Jan A., Oberley, Larry, Zhang, Yuping, Slingerland, Joyce, Arnold, Rebecca S., Lambeth, J. David, Cohen, Cynthia, Hilenski, Lu, Griendling, Kathy, Martínez-Díez, Marta, Cuezva, José M., and Arbiser, Jack L.
- Abstract
Melanoma is the cancer with the highest increase in incidence, and transformation of radial growth to vertical growth (i.e., noninvasive to invasive) melanoma is required for invasive disease and metastasis. We have previously shown that p42/p44 MAP kinase is activated in radial growth melanoma, suggesting that further signaling events are required for vertical growth melanoma. The molecular events that accompany this transformation are not well understood. Akt, a signaling molecule downstream of PI3K, was introduced into the radial growth WM35 melanoma in order to test whether Akt overexpression is sufficient to accomplish this transformation. Overexpression of Akt led to upregulation of VEGF, increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism. Subcutaneous implantation of WM35 cells overexpressing Akt led to rapidly growing tumors in vivo, while vector control cells did not form tumors. We demonstrated that Akt was associated with malignant transformation of melanoma through at least 2 mechanisms. First, Akt may stabilize cells with extensive mitochondrial DNA mutation, which can generate ROS. Second, Akt can induce expression of the ROS-generating enzyme NOX4. Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma
- Published
- 2007
12. Biogenesis and Dynamics of Mitochondria during the Cell Cycle: Significance of 39UTRs
- Author
-
Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Fundación Mutua Madrileña, Fundación Ramón Areces, Martínez-Díez, Marta, Santamaría, Gema, Ortega, Álvaro D., Cuezva, José M., Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Fundación Mutua Madrileña, Fundación Ramón Areces, Martínez-Díez, Marta, Santamaría, Gema, Ortega, Álvaro D., and Cuezva, José M.
- Abstract
Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of b-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (DYm) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of b-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 39UTR of the transcript. The 39UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated b-F1-ATPase expression in human cancer.
- Published
- 2006
13. Efficient execution of cell death in non-glycolytic cells requires the generation of ROS controlled by the activity of mitochondrial H+-ATP synthase
- Author
-
Ministerio de Ciencia y Tecnología (España), Ministerio de Sanidad y Consumo (España), Fundación Ramón Areces, Santamaría, Gema, Martínez-Díez, Marta, Fabregat, Isabel, Cuezva, José M., Ministerio de Ciencia y Tecnología (España), Ministerio de Sanidad y Consumo (España), Fundación Ramón Areces, Santamaría, Gema, Martínez-Díez, Marta, Fabregat, Isabel, and Cuezva, José M.
- Abstract
There is a large body of clinical data documenting that most human carcinomas contain reduced levels of the catalytic subunit of the mitochondrial H+-ATP synthase. In colon and lung cancer this alteration correlates with a poor patient prognosis. Furthermore, recent findings in colon cancer cells indicate that downregulation of the H+-ATP synthase is linked to the resistance of the cells to chemotherapy. However, the mechanism by which the H+-ATP synthase participates in cancer progression is unknown. In this work, we show that inhibitors of the H+-ATP synthase delay staurosporine (STS)-induced cell death in liver cells that are dependent on oxidative phosphorylation for energy provision whereas it has no effect on glycolytic cells. Efficient execution of cell death requires the generation of reactive oxygen species (ROS) controlled by the activity of the H+-ATP synthase in a process that is concurrent with the rapid disorganization of the cellular mitochondrial network. The generation of ROS after STS treatment is highly dependent on the mitochondrial membrane potential and most likely caused by reverse electron flow to Complex I. The generated ROS promote the carbonylation and covalent modification of cellular and mitochondrial proteins. Inhibition of the activity of the H+-ATP synthase blunted ROS production prevented the oxidation of cellular proteins and the modification of mitochondrial proteins delaying the release of cytochrome c and the execution of cell death. The results in this work establish the downregulation of the H+-ATP synthase, and thus of oxidative phosphorylation, as part of the molecular strategy adapted by cancer cells to avoid ROS-mediated cell death. Furthermore, the results provide a mechanistic explanation to understand chemotherapeutic resistance of cancer cells that rely on glycolysis as the main energy provision pathway.
- Published
- 2005
14. XPF-Dependent DNA Breaks and RNA Polymerase II Arrest Induced by Antitumor DNA Interstrand Crosslinking-Mimetic Alkaloids
- Author
-
Feuerhahn, Sascha, primary, Giraudon, Christophe, additional, Martínez-Díez, Marta, additional, Bueren-Calabuig, Juan A., additional, Galmarini, Carlos M., additional, Gago, Federico, additional, and Egly, Jean-Marc, additional
- Published
- 2011
- Full Text
- View/download PDF
15. Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer
- Author
-
Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología (España), Ministerio de Educación, Cultura y Deporte (España), Asociación Española Contra el Cáncer, National Institutes of Health (US), Fundación Ramón Areces, Isidoro, Antonio, Martínez-Díez, Marta, Fernández, Pedro L., Ortega, Álvaro D., Santamaría, Gema, Chamorro, Margarita, Reed, John C., Cuezva, José M., Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología (España), Ministerio de Educación, Cultura y Deporte (España), Asociación Española Contra el Cáncer, National Institutes of Health (US), Fundación Ramón Areces, Isidoro, Antonio, Martínez-Díez, Marta, Fernández, Pedro L., Ortega, Álvaro D., Santamaría, Gema, Chamorro, Margarita, Reed, John C., and Cuezva, José M.
- Abstract
Recent findings indicate that the expression of the beta-catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is depressed in liver, kidney and colon carcinomas, providing further a bioenergetic signature of cancer that is associated with patient survival. In the present study, we performed an analysis of mitochondrial and glycolytic protein markers in breast, gastric and prostate adenocarcinomas, and in squamous oesophageal and lung carcinomas. The expression of mitochondrial and glycolytic markers varied significantly in these carcinomas, when compared with paired normal tissues, with the exception of prostate cancer. Overall, the relative expression of beta-F1-ATPase was significantly reduced in breast and gastric adenocarcinomas, as well as in squamous oesophageal and lung carcinomas, strongly suggesting that alteration of the bioenergetic function of mitochondria is a hallmark of these types of cancer.
- Published
- 2003
16. Condiloma acuminado gigante (tumor de Buschke-Löwenstein)
- Author
-
Cuenca Marín, Celia, primary, Álvarez-Palencia Rueda, Cristina, additional, Ojeda Paredes, Dolores, additional, Martínez Díez, Marta, additional, Luna Ordóñez, Sergio, additional, and Martínez Martínez, Carlos, additional
- Published
- 2010
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.