8 results on '"Cortes-Sempere M"'
Search Results
2. IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer
- Author
-
Ibanez de Caceres, I, primary, Cortes-Sempere, M, additional, Moratilla, C, additional, Machado-Pinilla, R, additional, Rodriguez-Fanjul, V, additional, Manguán-García, C, additional, Cejas, P, additional, López-Ríos, F, additional, Paz-Ares, L, additional, de CastroCarpeño, J, additional, Nistal, M, additional, Belda-Iniesta, C, additional, and Perona, R, additional
- Published
- 2009
- Full Text
- View/download PDF
3. MKP1 repression is required for the chemosensitizing effects of NF-kappaB and PI3K inhibitors to cisplatin in non-small cell lung cancer.
- Author
-
Cortes-Sempere M, Chattopadhyay S, Rovira A, Rodriguez-Fanjul V, Belda-Iniesta C, Tapia M, Cejas P, Machado-Pinilla R, Manguan-García C, Sánchez-Pérez I, Nistal M, Moratilla C, de Castro-Carpeño J, Gonzalez-Barón M, Albanell J, Perona R, Cortes-Sempere, María, Chattopadhyay, Sharmila, Rovira, Ana, and Rodriguez-Fanjul, Vanessa
- Abstract
Treatment of non-small cell lung cancer (NSCLC) with cisplatin has a level of antitumor activity still modest. We have shown previously that MKP1/DUSP1 inhibits cisplatin-induced apoptosis in NSCLC cells and is overexpressed in tumors from most patients with stage I-II NSCLC. Here, using different NSCLC cell lines we found that MKP1 and NF-kappaB are differentially expressed. We studied whether targeting MKP1, NF-kappaB or both affects cisplatin-induced cell death. MKP1 is expressed in H460 and H727 cells. H727 and H1299 cells showed constitutive phosphorylation of Akt and increased NF-kappaB activity than did H460 cells. H460-MKP1-siRNA-expressing cells (but not H727-MKP1-siRNA or H1299-MKP1-siRNA cells) exhibit a marked increase in cisplatin response compared with parental cells. Treatment with the PI3K inhibitor LY294002 or the NF-kappaB inhibitor BAY11-7082 enhanced cisplatin antitumor activity in parental H1299 cells but only weakly affected responses of H727 and H460 cells. MKP1-siRNA expression enhanced the chemosensitization effect of LY294002 and BAY11-7082 on H727 and H460 cells. Additionally, NSCLC cell lines with higher NF-kappaB-constitutive activation were the most sensitive to PS-341 (Bortezomib), a non-specific NF-kappaB inhibitor. This finding suggests the proteasome as a suitable strategy in treating NSCLC tumors with high constitutive NF-kappaB activity. Altogether, these results showed that either an activated PI3K/Akt/NF-kappaB pathway and/or high MKP1 was linked to reduced sensitivity to cisplatin in NSCLC cells. Inhibition of NF-kappaB or PI3K potently enhanced cisplatin cytotoxicity in cells with endogenous or genetically induced low MKP1 levels. These findings support the potential improvement in cisplatin responses by co-targeting NF-kappaB or Akt and MKP1. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
4. Differential expression of DNAmethyltransferases in sensitive versus cisplatin resistant NSCLC cell lines
- Author
-
Cortés-Sempere, M., Perona, R., and Ibanez de Caceres, I.
- Published
- 2008
- Full Text
- View/download PDF
5. Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer.
- Author
-
Moncho-Amor V, Pintado-Berninches L, Ibañez de Cáceres I, Martín-Villar E, Quintanilla M, Chakravarty P, Cortes-Sempere M, Fernández-Varas B, Rodriguez-Antolín C, de Castro J, Sastre L, and Perona R
- Subjects
- Actin Cytoskeleton metabolism, Adenocarcinoma of Lung enzymology, Adenocarcinoma of Lung pathology, Adherens Junctions metabolism, Animals, Carcinogenesis genetics, Carcinogenesis pathology, Carcinoma, Non-Small-Cell Lung pathology, Cell Adhesion genetics, Cell Line, Tumor, Cell Movement genetics, Cell Shape genetics, Disease Progression, Dual Specificity Phosphatase 6 metabolism, Focal Adhesions metabolism, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Lung Neoplasms pathology, MAP Kinase Signaling System, Mice, Nude, Transforming Growth Factor beta metabolism, Carcinoma, Non-Small-Cell Lung enzymology, Carcinoma, Non-Small-Cell Lung genetics, Dual Specificity Phosphatase 6 genetics, Genes, Tumor Suppressor, Lung Neoplasms enzymology, Lung Neoplasms genetics
- Abstract
DUSP6/MKP3 is a dual-specific phosphatase that regulates extracellular regulated kinase ERK1/2 and ERK5 activity, with an increasingly recognized role as tumor suppressor. In silico studies from Gene expression Omnibus (GEO) and Cancer Genome atlas (TCGA) databases reveal poor prognosis in those Non-small cell lung cancer (NSCLC) patients with low expression levels of DUSP6 . In agreement with these data, here we show that DUSP6 plays a major role in the regulation of cell migration, motility and tumor growth. We have found upregulation in the expression of several genes involved in epithelial to mesenchymal transition (EMT) in NSCLC- DUSP6 depleted cells. Data obtained in RNA-seq studies carried out in DUSP6 depleted cells identified EGFR, TGF-β and WNT signaling pathways and several genes such as VAV3, RUNXR2, LEF1, FGFR2 whose expression is upregulated in these cells and therefore affecting cellular functions such as integrin mediated cell adhesion, focal adhesion and motility. Furthermore, EGF signaling pathway is activated via ERK5 and not ERK1/2 and TGF-β via SMAD2/3 in DUSP6 depleted cells. In summary DUSP6 is a tumor suppressor in NSCLC and re-establishment of its expression may be a potential strategy to revert poor outcome in NSCLC patients.
- Published
- 2019
- Full Text
- View/download PDF
6. High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response.
- Author
-
Arrizabalaga O, Moreno-Cugnon L, Auzmendi-Iriarte J, Aldaz P, Ibanez de Caceres I, Garros-Regulez L, Moncho-Amor V, Torres-Bayona S, Pernía O, Pintado-Berninches L, Carrasco-Ramirez P, Cortes-Sempere M, Rosas R, Sanchez-Gomez P, Ruiz I, Caren H, Pollard S, Garcia I, Sacido AA, Lovell-Badge R, Belda-Iniesta C, Sampron N, Perona R, and Matheu A
- Abstract
The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC. Notably, we find that high levels of MKP1 correlate with a subset of glioblastoma patients with better prognosis and overall increased survival. Gain of expression studies demonstrated that elevated MKP1 impairs self-renewal and induces differentiation of GSCs while reducing tumorigenesis in vivo. Moreover, we identified that MKP1 is epigenetically regulated and that it mediates the anti-tumor activity of histone deacetylase inhibitors (HDACIs) alone or in combination with temozolomide. In summary, this study identifies MKP1 as a key modulator of the interplay between GSC self-renewal and differentiation and provides evidence that the activation of MKP1, through epigenetic regulation, might be a novel therapeutic strategy to overcome therapy resistance in glioblastoma.
- Published
- 2017
- Full Text
- View/download PDF
7. Methylation status of IGFBP-3 as a useful clinical tool for deciding on a concomitant radiotherapy.
- Author
-
Pernía O, Belda-Iniesta C, Pulido V, Cortes-Sempere M, Rodriguez C, Vera O, Soto J, Jiménez J, Taus A, Rojo F, Arriola E, Rovira A, Albanell J, Macías MT, de Castro J, Perona R, and Ibañez de Caceres I
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung surgery, Cell Line, Tumor radiation effects, Cell Survival genetics, Cell Survival radiation effects, Combined Modality Therapy, DNA Methylation, Female, Humans, Insulin-Like Growth Factor Binding Protein 3 genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms mortality, Lung Neoplasms surgery, Male, Middle Aged, Phosphorylation drug effects, Prognosis, Proto-Oncogene Proteins c-akt metabolism, Survival Analysis, Treatment Outcome, Carcinoma, Non-Small-Cell Lung radiotherapy, Insulin-Like Growth Factor Binding Protein 3 metabolism, Lung Neoplasms radiotherapy, Promoter Regions, Genetic
- Abstract
The methylation status of the IGFBP-3 gene is strongly associated with cisplatin sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we found in vitro evidence that linked the presence of an unmethylated promoter with poor response to radiation. Our data also indicate that radiation might sensitize chemotherapy-resistant cells by reactivating IGFBP-3-expression through promoter demethylation, inactivating the PI3K/AKT pathway. We also explored the IGFBP-3 methylation effect on overall survival (OS) in a population of 40 NSCLC patients who received adjuvant therapy after R0 surgery. Our results indicate that patients harboring an unmethylated promoter could benefit more from a chemotherapy schedule alone than from a multimodality therapy involving radiotherapy and platinum-based treatments, increasing their OS by 2.5 y (p = .03). Our findings discard this epi-marker as a prognostic factor in a patient population without adjuvant therapy, indicating that radiotherapy does not improve survival for patients harboring an unmethylated IGFBP-3 promoter.
- Published
- 2014
- Full Text
- View/download PDF
8. Mitogen-activated protein kinase phosphatase-1 in human breast cancer independently predicts prognosis and is repressed by doxorubicin.
- Author
-
Rojo F, González-Navarrete I, Bragado R, Dalmases A, Menéndez S, Cortes-Sempere M, Suárez C, Oliva C, Servitja S, Rodriguez-Fanjul V, Sánchez-Pérez I, Campas C, Corominas JM, Tusquets I, Bellosillo B, Serrano S, Perona R, Rovira A, and Albanell J
- Subjects
- Antibiotics, Antineoplastic pharmacology, Blotting, Western, Breast Neoplasms genetics, Breast Neoplasms metabolism, Cell Line, Tumor, Cluster Analysis, Dual Specificity Phosphatase 1 genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression Regulation, Enzymologic drug effects, Gene Expression Regulation, Neoplastic drug effects, Humans, Immunohistochemistry, In Vitro Techniques, JNK Mitogen-Activated Protein Kinases metabolism, Kaplan-Meier Estimate, Neoplasm Recurrence, Local, Phosphorylation drug effects, Predictive Value of Tests, Prognosis, Reverse Transcriptase Polymerase Chain Reaction, p38 Mitogen-Activated Protein Kinases metabolism, Breast Neoplasms pathology, Doxorubicin pharmacology, Dual Specificity Phosphatase 1 metabolism
- Abstract
Purpose: Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) dephosphorylates mitogen-activated protein kinase [extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38], mediates breast cancer chemoresistance, and is repressible by doxorubicin in breast cancer cells. We aimed to characterize doxorubicin effects on MKP-1 and phospho-MAPKs in human breast cancers and to further study the clinical relevance of MKP-1 expression in this disease., Experimental Design: Doxorubicin effects on MKP-1, phospho-ERK1/2 (p-ERK1/2), phospho-JNK (p-JNK), and phospho-p38 were assayed in a panel of human breast cancer cells by Western blot and in human breast cancer were assayed ex vivo by immunohistochemistry (n = 50). MKP-1 expression was also assayed in a range of normal to malignant breast lesions (n = 30) and in a series of patients (n = 96) with breast cancer and clinical follow-up., Results: MKP-1 was expressed at low levels in normal breast and in usual ductal hyperplasia and at high levels in in situ carcinoma. MKP-1 was overexpressed in approximately 50% of infiltrating breast carcinomas. Similar to what was observed in breast cancer cell lines, ex vivo exposure of breast tumors to doxorubicin down-regulated MKP-1, and up-regulated p-ERK1/2 and p-JNK, in the majority of cases. However, in a proportion of tumors overexpressing MKP-1, doxorubicin did not significantly affect MKP-1 or phospho-MAPKs. With regard to patient outcome, MKP-1 overexpression was an adverse prognostic factor for relapse both by univariate (P < 0.001) and multivariate analysis (P = 0.002)., Conclusions: MKP-1 is overexpressed during the malignant transformation of the breast and independently predicts poor prognosis. Furthermore, MKP-1 is repressed by doxorubicin in many human breast cancers.
- Published
- 2009
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.