A5008409708- Cancer Cells and Metastasis
- Genetic factors in colorectal cancer
- 3D Printing in Biomedical Research
- Cancer, Lipids, and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- Microbial metabolism and enzyme function
- Inflammatory mediators and NSAID effects
- DNA Repair Mechanisms
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Cancer-related gene regulation
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Wnt/β-catenin signaling in development and cancer
- Inflammatory Biomarkers in Disease Prognosis
- Colorectal and Anal Carcinomas
- Cholangiocarcinoma and Gallbladder Cancer Studies
- MicroRNA in disease regulation
- Cancer Treatment and Pharmacology
Instituto Ramón y Cajal de Investigación Sanitaria
2018-2024
Instituto Cajal
2018-2023
Centro de Investigación Biomédica en Red de Cáncer
2018-2023
INCLIVA Health Research Institute
2023
Ponce Health Sciences University
2023
Centro Oncológico de Galicia
2023
Universidad Alfonso X el Sabio
2022
Hospital Universitario La Paz
2019-2021
Hospital Universitario Ramón y Cajal
2020
Hospital Universitario Puerta de Hierro Majadahonda
2007-2018
Expression of Snail1 in epithelial cells triggers an epithelial–mesenchymal transition (EMT). Here, we demonstrate that the synthesis Zeb2, a transcriptional repressor E-cadherin, is up-regulated after Snail1-induced EMT. does not affect Zeb2 mRNA, but prevents processing large intron located its 5′-untranslated region (UTR). This contains internal ribosome entry site (IRES) necessary for expression Zeb2. Maintenance 5′-UTR dependent on natural antisense transcript (NAT) overlaps 5′ splice...
Abstract A significant proportion of extracellular nucleic acids in plasma circulate highly protected tumor‐specific exosomes, but it is unclear how the release exosomes modulated carcinogenesis. We quantified by cytometry 91 colorectal cancer patients to evaluate their potential as a tumor indicator and repercussions on diagnosis prognosis. examined involvement TSAP6 , TP53 ‐regulated gene involved regulation vesicular secretion, levels circulating HCT116 ‐(wild‐type null) human cell lines....
The identification of tumour biomarkers that detect the presence disease using noninvasive diagnostic procedures is a key part cancer research. We determined in plasma vesicle-related microRNA (miRNA) expression profile nonsmall cell lung (NSCLC) and evaluate whether miRNAs can be both discriminating (between patients healthy controls) prognostic markers. 365 human were analysed by Taqman® low-density arrays (Applied Biosystems, Foster City, CA, USA) from 28 NSCLC 20 controls. Five selected...
Tumor epithelial cells within a tumor coexist with complex microenvironment in which variety of interactions between its various components determine the behavior primary tumors. Cancer‐associated fibroblasts ( CAF ) and M 2 macrophages, characterized by high expression different markers, including α‐ SMA , FSP 1 FAP or CD 163 DCSIGN respectively, are involved malignancy In present study, above markers macrophages was analyzed using RT ‐ PCR immunohistochemistry normal mucosa tissue from...
Abstract Purpose: Cancer-associated fibroblasts (CAF) are essential components of the stroma that play a critical role in cancer progression. This study aimed to identify novel CAFs markers might contribute invasion and prognosis colorectal cancer. Experimental Design: The azoxymethane/dextran sodium sulfate mouse model sporadic colon represents an adequate source for isolation normal fibroblasts. By using explants technique, we purified from tissues. Whole-cell extracts supernatants were...
Abstract MicroRNAs (miRNAs) are noncoding RNAs that regulate expression of target mRNAs and controlled by tumor suppressors oncogenes. Altered specific miRNAs in several types its association with poor prognosis parameters have been reported. Fewer data available on impact patients' survival. We studied the miR‐17‐5p , miR‐106a miR‐126 survival correlation levels their host gene TP53 alterations. assessed 110 colon cancer patients E2F1 EGFL7 quantitative real‐time RT‐PCR loss heterozygosity...
Abstract About 25–50% of women with Cowden disease, a syndrome associated germ‐line mutations the PTEN gene (at 10q23), develop breast cancer (BC), but have been found in only 5% sporadic BCs. However, 29–48% BCs display loss heterozygosity 10q23, and about 40% show decrease or absence protein levels at time diagnosis. Promoter hypermethylation has identified as an alternative mechanism tumor‐suppressor inactivation, its importance silencing BC is unknown. We investigated promoter 90...
E-cadherin (CDH1) gene expression is strictly regulated. The transcriptional factors SNAIL and ZEB1 are involved in its repression, whereas activation of vitamin D receptor (VDR) by induces transcription. We study the functional correlation SNAIL, CDH1, VDR genes examine their possible involvement colon cancer. these four was measured real time-PCR 114 patients with colorectal cancer, tumor characteristics were analyzed each patient. associated downregulation CDH1 (P<0.001) products. also...
The Wnt-beta-catenin pathway is aberrantly activated in most colon cancers. DICKKOPF-1 (DKK-1) gene encodes an extracellular Wnt inhibitor that blocks the formation of signalling receptor complexes at plasma membrane. We report 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], active vitamin D metabolite, increases level DKK-1 RNA and protein human SW480-ADH cancer cells. This effect dose dependent, slow depends on presence a transcription-competent nuclear (VDR). Accordingly, 1,25(OH)2D3...
<h3>Objective</h3> Colorectal cancer (CRC) is a major health concern. Vitamin D deficiency associated with high CRC incidence and mortality, suggesting protective effect of vitamin against this disease. Given the strong influence tumour stroma on progression, we investigated potential effects active metabolite 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) stroma. <h3>Design</h3> Expression receptor (VDR) two 1,25(OH)<sub>2</sub>D<sub>3</sub> target genes was...
Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression PDGF receptors on stromal CAFs associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification secreted glycoprotein stanniocalcin-1 (STC1) as mediator by function in setting colorectal cancer. PDGF-stimulated increased migration invasion cocultured cancer...
Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and other cell types the microenvironment, contributing to a tumor-permissive neighborhood promoting progression. The aim of this study is characterization how CAFs from primary human colon tumors promote migration cancer cells.Primary CAF cultures 15 were established. Their enrichment was evaluated by expression various epithelial myofibroblast specific markers. Coculture assays different...
Tumor‐derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes plasma BAL 30 75 nontumor pathology were quantified acetylcholinesterase activity characterized Western Blot, Electron Microscopy, Nanoparticle Tracking Analysis. Differences exosome cargo analyzed miRNA quantitative PCR pooled samples...
Crosstalk between tumor and stromal cells in the microenvironment alter its properties ways that facilitate invasive behavior of cells. Here, we demonstrate cancer-associated fibroblasts (CAF) increase stiffness extracellular matrix (ECM) promote anisotropic fiber orientation, two mechanical signals generated through a Snail1/RhoA/αSMA-dependent mechanism sustains oriented cell migration invasiveness. Snail1-depleted CAF failed to acquire myofibroblastic traits response TGFβ, including RhoA...
Abstract Purpose: Cancer-associated fibroblasts (CAF) are major mediators in tumor microenvironment. We investigated the changes protein expression colon cancer–associated compared with normal (NF) context of searching for prognostic biomarkers, particularly stage II patients. Experimental Design: CAFs and NFs isolated from cancer patients were used to identify differentially expressed proteins using quantitative proteomics. Stromal deregulated was analyzed by IHC. Prognostic impact studied...
Abstract ZEB1 and SNAIL repress CDH1 induce epithelial–mesenchymal transition (EMT). However, also activate or regulate other target genes in different ways. For instance, vitamin D receptor (VDR), which activates expression upon ligand binding, is repressed by but induced ZEB1. We examined whether the biological activity of colon cancer regulated interacting cofactors. The mRNA levels , transcriptional regulators p300 CtBP, were measured RT‐PCR tumor normal tissue from 101 carcinoma...
Vitamin D receptor (VDR) mediates the antitumoral action of active vitamin metabolite 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). VDR expression is lost during colon cancer progression causing unresponsiveness to 1,25(OH)(2)D(3) and its analogs. Previously, Snail1, an inducer epithelial-to-mesenchymal transition (EMT), was reported inhibit expression. Here, we show that Snail2/Slug, but not other EMT inducers such as Zeb1, Zeb2, E47 or Twist1, represses gene promoter. Moreover, Snail2...
The active vitamin D metabolite 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] has wide but not fully understood antitumor activity. A previous transcriptomic analysis of 1alpha,25(OH)2D3 action on human colon cancer cells revealed cystatin (CST5), which encodes an inhibitor several cysteine proteases the cathepsin family, as a candidate target gene. Here we report that induced receptor (VDR) binding to, and activation of, CST5 promoter increased RNA protein levels in cells. In lacking...
Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target hedgehog signaling, known regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain- loss-of-function revealed...
Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, growth, angiogenesis metastasis. Here we analyzed the exosomes release by breast tumor with different capacities of stemness/metastasis based on CXCR4 expression, evaluated their capacity generate oncogenic features in recipient cells. Breast cancer overexpressing showed an increase stemness-related markers, proliferation, migration invasion capacities....
Abstract Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an EMT-independent action of on invasion, as it required the activation cancer-associated fibroblasts (CAF). expression in requires signals derived from cells, such TGFβ; reciprocally, fibroblasts, organizes a complex program that stimulates invasion epithelial cells independent these cells. Epithelial stimulated by secretion...