A5047574440- Liver physiology and pathology
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Cellular Mechanics and Interactions
- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- TGF-β signaling in diseases
- Pancreatic function and diabetes
- Lymphatic System and Diseases
- Allergic Rhinitis and Sensitization
- Melanoma and MAPK Pathways
- Entomological Studies and Ecology
- Protist diversity and phylogeny
- Microtubule and mitosis dynamics
- Connective tissue disorders research
- Aortic aneurysm repair treatments
- HER2/EGFR in Cancer Research
- Aortic Disease and Treatment Approaches
- Prostate Cancer Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- Adenosine and Purinergic Signaling
- Chemokine receptors and signaling
- Macrophage Migration Inhibitory Factor
Queen Mary University of London
2019-2025
Breast Cancer Now
2024-2025
Institute of Cancer Research
2024-2025
King's College London
2016-2025
Institut d'Investigació Biomédica de Bellvitge
2013-2024
Bellvitge University Hospital
2014-2024
Instituto de Salud Carlos III
2021
Cancer Research UK
2019
Universitat de Barcelona
2015
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2015
ROCK-Myosin II drives fast rounded-amoeboid migration in cancer cells during metastatic dissemination. Analysis of human melanoma biopsies revealed that amoeboid with high Myosin activity are predominant the invasive fronts primary tumors proximity to CD206+CD163+ tumor-associated macrophages and vessels. Proteomic analysis shows controls an immunomodulatory secretome, enabling recruitment monocytes their differentiation into tumor-promoting macrophages. Both associated support abnormal...
A role for the NADPH oxidases NOX1 and NOX2 in liver fibrosis has been proposed, but implication of NOX4 is poorly understood yet. The aim this work was to study functional different cell populations implicated fibrosis: hepatic stellate cells (HSC), myofibroblats (MFBs) hepatocytes. Two mice models that develop spontaneous (Mdr2−/−/p19ARF−/−, Stat3Δhc/Mdr2−/−) a model experimental induced (CCl4) were used. In addition, gene expression biopsies from chronic hepatitis C virus (HCV) patients...
Marfan's syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly extracellular matrix microfibrils and chronic tissue growth factor (TGF)-β signaling. TGF-β a potent regulator vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as result signaling, VSMC would alter their basal differentiation phenotype, which could facilitate aneurysms. This study explores whether entails phenotypic alterations possible mechanisms at subcellular...
Despite substantial clinical benefit of targeted and immune checkpoint blockade-based therapies in melanoma, resistance inevitably develops. We show cytoskeletal remodeling changes expression activity ROCK-myosin II pathway during acquisition to MAPK inhibitors. regulates myosin activity, but after initial therapy response, drug-resistant clones restore increase survival. High correlates with aggressiveness, identifying therapy- immunotherapy-resistant melanomas. Survival resistant cells is...
Transforming growth factor-beta (TGF-β) is an important regulatory suppressor factor in hepatocytes. However, liver tumor cells develop mechanisms to overcome its effects and respond this cytokine by inducing other processes, such as the epithelial-mesenchymal transition (EMT), which contributes progression dissemination. Recent studies have placed chemokines their receptors at center not only of physiological cell migration but also pathological metastasis cancer. In particular, CXCR4...
Abstract Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cells exert low adhesion/low traction linked to ATP/AMP, leading AMPK activation. turn, plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High activity in adhering migratory cells, induces fission, resulting lower oxidative phosphorylation...
The extracellular matrix (ECM) controls tumour dissemination. We characterise ECM organization in human and mouse tumours, identifying three regions: body, proximal invasive front distal front. Invasive areas show increased density, fibre thickness, length, alignment, with unique radial orientation at the correlating amoeboid features. Using patient samples murine models, we find that metastases recapitulate features of primary tumour. Ex vivo culture cancer cells isolated from different...
Epithelial to mesenchymal transition is a common event during tumour dissemination. However, direct epithelial amoeboid has not been characterized date. Here we provide evidence that cells from hepatocellular carcinoma (HCC), highly metastatic cancer, undergo in physiological environments, such as organoids or three-dimensional complex matrices. Furthermore, the NADPH oxidase NOX4 inhibits this and therefore suppresses efficient bleb-based invasion. Moreover, expression associated with...
The NADPH oxidase NOX4 plays a tumor-suppressor function in HCC. Silencing confers higher proliferative and migratory capacity to HCC cells increases their vivo tumorigenic potential xenografts mice. gene deletions are frequent HCC, correlating with tumor grade worse recurrence-free overall survival rates. However, despite the accumulating evidence of protective regulatory role cellular processes governed by not yet understood. Accordingly, aim this work was better understand molecular...
Different data support a role for the epidermal growth factor receptor (EGFR) pathway during liver regeneration and hepatocarcinogenesis. However, important issues, such as precise mechanisms mediating its actions unique versus redundant functions, have not been fully defined. Here, we present novel transgenic mouse model expressing hepatocyte‐specific truncated form of human EGFR, which acts negative dominant mutant (ΔEGFR) allows definition tyrosine kinase–dependent functions. Results...
Abstract The PPARγ coactivator 1 alpha (PGC1α) is a prostate tumor suppressor that controls the balance between anabolism and catabolism. PGC1A downregulation in cancer causally associated with development of metastasis. Here we show transcriptional complex formed by PGC1α estrogen-related receptor (ERRα) aggressive properties cells. expression significantly decreased migration invasion various cell lines. This phenotype was consistent remarkable cytoskeletal remodeling inhibition integrin...
The Epidermal Growth Factor Receptor (EGFR) and the Transforming Factor-beta (TGF-β) are key regulators of hepatocarcinogenesis. Targeting EGFR was proposed as a promising therapy; however, poor success obtained in human hepatocellular carcinoma (HCC) clinical trials. Here, we describe how is frequently downregulated HCC patients while TGF-β upregulated. Using 2D/3D cellular models, show that after loss, more efficient its pro-migratory invasive effects, inducing epithelial to amoeboid...
Liver is a unique organ in displaying reparative and regenerative response after acute/chronic damage or partial hepatectomy, when all the cell types must proliferate to re-establish liver mass. The NADPH oxidase NOX4 mediates Transforming Growth Factor-beta (TGF-β) actions, including apoptosis hepatocytes activation of stellate cells myofibroblasts. Aim this work was analyze impact regeneration by using two mouse models where Nox4 deleted: 1) general deletion (NOX4-/-) 2)...
Abstract Background Metastasis is a hallmark of cancer and responsible for most deaths. Migrastatics were defined as drugs interfering with all modes cell invasion thus cancers’ ability to metastasise. First anti-metastatic treatments have recently been approved. Methods We used bioinformatic analyses publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D morphology analysis mass spectrometric RhoA binding partners), developed new...
Melanoma is an aggressive skin cancer developing from melanocytes, frequently resulting in metastatic disease. cells utilize amoeboid migration as mode of local invasion. Amoeboid invasion characterized by rounded cell morphology and high actomyosin contractility driven Rho GTPase signalling. Migrastatic drugs targeting actin polymerization are therefore a promising treatment option for melanoma. To predict potential, biomarkers functionally linked to pathways needed. The glycoprotein...
Cell migration plays a pivotal role in various biological processes including cancer dissemination and successful metastasis, where the of mechanical signals is increasingly acknowledged. This review focuses on intricate mechanisms through which cells modulate their migratory strategies via organelle adaptations response to extracellular matrix (ECM). Specifically, nucleus mitochondria emerge as mediators this process. These organelles serve sensors, translating stimuli into rapid metabolic...
For decades, reactive oxygen species (ROS) linked to oxidative stress have been suggested promote carcinogenesis. However, we and others demonstrated a protective role for ROS in metastatic dissemination. These recent studies partly explain the large failure observed clinical trials using antioxidants cancer prevention.