Mechanisms of Tumorigenesis and Tumor Progression
<
Cancer Programme
The group’s interest is the study of the mechanisms controlling the acquisition of invasiveness by epithelial tumours as the first step in tumour metastasis. We are currently investigating several aspects of this process, such as epithelial-to-mesenchymal transition (EMT), a conversion that provides tumour cells with more invasion and also resistance to chemotherapeutic drugs.
We are especially analysing the role of Snail1 transcriptional factor, required for EMT and also necessary for the activation of cancer-associated fibroblasts (CAFs). We are currently studying how Snail1 expression is regulated both transcriptionally and post-translationally, since Snail1 protein half-life is finely tuned. Moreover, using CAFs deprived of Snail1, we are assessing the effect of CAF activation in the growth, invasion, and immune response of epithelial tumours. We are also interested in the Snail1-dependent molecular pathways in fibroblasts involved in the activation of tumour cell invasion. Finally, we are also investigating the role of Snail1 in other tumour microenvironment cells, such as endothelial cells.
A second line of research is led by Dr. Pilar Navarro within a framework partnership agreement with the Institute of Biomedical Research of Barcelona (Associated Unit IMIM-IIBB CSIC, created in June 2018) and is focused on exploring other molecular mechanisms underlying tumor progression; specifically, the relevance of galectin-mediated tumour-stroma crosstalk. Moreover, considering that cancer is a genetic disease caused by changes in gene expression during malignant transformation, we are also very interested in deciphering how these genetic changes are regulated by RNA translational control.
The research group was recognized by AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya) as a research group (2017 SGR 24; Principal investigator: Antonio García de Herreros Madueño).
Research group
Members
Luis Eugenio Barranco Priego (Researcher)
Josep Baulida Estadella (Researcher)
Beatriz del Valle Pérez (Researcher)
Gemma Mancebo Moreno (Researcher)
Neus Martínez Bosch (Researcher)
Marina Bruch Oms (PhD Student)
David Cabrerizo Granados (PhD Student)
Héctor Franco Valls (PhD Student)
Aida Mestre Farrera (PhD Student)
Raúl Martínez Izquierdo (Technician)
Mireia Moreno Merino (Technician)
Raúl Peña Arranz (Technician)
Silvia Geeraerd (Research Assistant)
Main Publications
• Martínez-Bosch N, Rodríguez-Vida A, Juanpere N, Lloreta J, Rovira A, Albanell J, Bellmunt J, Navarro P. Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities. Nat Rev Urol. 2019; 16(7): 433-445. IF 9.333. D1.
• Lambies G, Miceli M, Martínez-Guillamon C, Olivera-Salguero R, Peña R, Frías CP, Calderon I, Atanassov BS, Dent SYR, Arribas J, García de Herreros A, Díaz VM. TGFβ-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. Cancer Res 2019; 79(1): 33-46. IF 8.378. Q1.
• Baulida J, Díaz VM, García de Herreros A. Snail1: a transcriptional factor controlled at multiple levels. J, Clin. Med 219; 8(6): E757. IF 5.688. D1.
• Sala-Romanyà L, Franco-Valls H, Stanisavljevic J, Curto J, Vergés J, Peña R, Duch P, Alcaraz J, García de Herreros A, Baulida J. Abrogation of myofibroblast activities in metastasis and fibrosis by methyltransferase inhibition. Int J Cancer 2019; 145(11): 3064-3077. IF 4.982. Q1.
• García de Herreros A, Duñach M. Intracellular Signals Activated by Canonical Wnt Ligands Independent of GSK3 Inhibition and β-Catenin Stabilization. Cells 2019, 8(10): E1148. IF 4.829. Q1.
Ongoing Research Projects
• Entendiendo el papel de Snail1 en la metástasis: análisis de la acción de los fibroblastos activos
- Financing institution: Ministerio de Economía y Competitividad (SAF2016-76461-R)
- Period: From 2016 to 2019
- Principal investigator: García de Herreros Madueño, Antonio
Clinical Trials Signed in 2019
• Ensayo Clínico PALOMA II: Ensayo clínico, aleatorizado, abierto, muticéntrico, de grupos paralelos y con grupo control, para la evaluación del efecto de PAPILOCARE® en la normalización de las alteraciones citológicas del cuello del útero causadas por el Virus Papiloma Humano
- Protocol: PALOMA II
- Sponsor: Procare Health Iberia, S.L.
- Budget: 9,450 €
- Principal investigator: Mancebo Moreno, Gemma; Solé Sedeño, Josep Maria
Theses
• Lambies G. Deubiquitinating enzymes stabilizing Snail1 transcription factor: a role for USP27X in epithlia. Universitat Pompeu Fabra
- Directors: Díaz VM, García de Herreros Madueño, Antonio
- Date of defense: 10/01/2019
• Olivera R. New roles for Snail1 expressing Cancer-Associated Fibroblasts (CAFs) during primary tumor progression and secondary niche colonization. Universitat Pompeu Fabra
- Director: García de Herreros Madueño, Antonio
- Date of defense: 19/07/2019