Mechanisms of Tumorigenesis and Tumor Progression

 Research group

Group Leader

Antonio García de Herreros Madueño

The group focuses on the study of the mechanisms controlling the acquisition of invasiveness by epithelial tumors as the first step in tumor metastasis. We are currently studying several aspects of this process.  The main interest of the group concerns epithelial-to-mesenchymal transition (EMT), a conversion that provides tumor cells with greater invasive capacity, resistance to chemotherapeutic drugs, and cancer stem characteristics. In particular, we analyze the role of Snail1 transcriptional factor, required for EMT and also necessary for the activation of cancer-associated fibroblasts (CAFs). We are studying how Snail1 is post-translationally activated during EMT. Moreover, using CAFs deprived of Snail1, we are assessing the effect of CAF activation on the growth, invasion and vascularization of epithelial tumors. We are also interested in the Snail1-dependent molecular pathways in fibroblasts involved in the activation of tumor cell invasion. In addition, we explore other molecular mechanisms underlying tumor progression, specifically the relevance of galectin-mediated tumor-stroma crosstalk. Moreover, given 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.

Members

Luis Eugenio Barranco Priego (Researcher)

Josep Baulida Estadella (Researcher)

Víctor Manuel Díaz Cortés (Researcher)

Gemma Mancebo Moreno (Researcher)

Neus Martínez Moreno (Researcher)

Marina Bruch Oms (PhD Student)

David Cabrerizo Granados (PhD Student)

Héctor Franco Valls (PhD Student)

Guillem Lambies Barjau (PhD Student)

Aida Mestre Farrera (PhD Student)

Rubén Olivera Salguero (PhD Student)

Judit Vinaixa Forner (PhD Student)

Noemí Manero Rupérez (Technician)

Mireia Moreno Merino (Technician)

Raul Peña Arranz (Technician)

Jordi Vergés Sanjaime (Technician)

Silvia Geeraerd (Research assistant)

 

Main Publications

• Parras A, Anta H, Santos-Galindo M, Swarup V, Elorza A, Nieto-González JL, Picó S, Hernández IH, Díaz-Hernández JI, Belloc E, Rodolosse A, Parikshak NN, Peñagarikano O, Fernández-Chacón R, Irimia M, Navarro P, Geschwind DH, Méndez R, Lucas JJ. Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing. Nature 2018; 560(7719): 441-446. IF 41.577. D1.

• Pascual-Reguant L, Blanco E, Galán S, Le Dily F, Cuartero Y, Serra-Bardenys G, Di Carlo V, Iturbide A, Cebrià-Costa JP, Nonell L, García de Herreros A, Di Croce L, Martí-Renom MA, Peiró S. Lamin B1 mapping reveals the existence of dynamic and functional euchromatin lamin B1 domains. Nat Commun 2018; 9(1): 3420. IF 12.353. D1.

• Mazzolini R, González N, García-Garijo A, Millanes-Romero A, Peiró S, Smith S, García de Herreros A, Canudas S. Snail1 transcription factor controls telomere transcription and integrity. Nucleic Acids Res 2018; 46(1): 146-158. IF 11.561. D1.

• Orozco CA, Martínez-Bosch N, Guerrero PE, Vinaixa J, Dalotto-Moreno T, Iglesias M, Moreno M, Djurec M, Poirier F, Gabius HJ, Fernández-Zapico ME, Hwang RF, Guerra C, Rabinovich GA, Navarro P. Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk. Proc Natl Acad Sci U S A 2018; 115(16): E3769-E3778. IF 9.504. D1.

• Martínez-Bosch N, Vinaixa J, Navarro P. Immune Evasion in Pancreatic Cancer: From Mechanisms to Therapy. Cancers 2018; 10(1): 6. IF 5.326. Q1.

• Curto J, Del Valle B, Villarroel A, Fuertes G, Vinyoles M, Peña R, García de Herreros A, Duñach M. CK1ε and p120-catenin control Ror2 function in non-canonical Wnt signaling. Mol Oncol 2018; 12(5): 611-629. IF 5.264. Q1.

• Herrera A, Herrera M, Guerra-Pérez N, Galindo-Pumariño C, Larriba MJ, García-Barberán V, Gil B, Giménez-Moyano S, Ferreiro-Monteagudo R, Veguillas P, Candia A, Peña R, Pinto J, García-Bermejo ML, Muñoz A, García de Herreros A, Bonilla F, Carrato A, Peña C. Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1. Oncogenesis 2018; 7(9): 76. IF 4.722. Q1.

• Martínez-Bosch N; Barranco LE; Orozco CA; Moreno M; Visa L; Iglesias M; Oldfield L; Neoptolemos JP; Greenhalf W; Earl J; Carrato A; Costello E; Navarro P. Increased plasma levels of galectin-1 in pancreatic cancer: potential use as biomarker. Oncotarget. 9: 32984 - 32996. IF 4.67. Q1.

• Farfán N, Ocarez N, Castellón EA, Mejía N, García de Herreros A, Contreras HR. The transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer. Sci Rep 2018; 8(1): 11467. IF 4.122. Q1.

• Goday A, Castañer O, Benaiges D, Busquets-Pou A, Ramon-Moros JM, Iglesias M, Barranco L, Flores JA. Can Helicobacter pylori Eradication Treatment Modify the Metabolic Response to Bariatric Surgery?. Obes Surg 2018; 28(8): 2386-2395. IF 3.895. D1.

Ongoing Research Projects

• Identificación de nuevos mecanismos de regulación de la hemostasia: control de la función plaquetaria a través de la proteína CPEB4

- Financing institution: Fundación Española de Trombosis y Hemostasia (FETH)

- Period: from 2018 to 2019.

- Principal investigator: Navarro Medrano, Pilar

• Galectinas, control de la expresión génica y cáncer: de los mecanismos moleculares a la práctica clínica

- Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI17/00199)

- Period: 2018

- Principal investigator: Navarro Medrano, Pilar

• Entendiendo el papel de Snail1 en la metastasis: 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

• Galectina-1: una nueva diana para el desarrollo de herramientas diagnósticas y terapéuticas para el cáncer de páncreas

- Financing institution: Asociación Cáncer de Páncreas

- Period: from 2016 to 2019

- Principal investigator: Navarro Medrano, Pilar

• Caracterización de dianas funcionales e inhibidores de la actividad miofibroblástica para frenar la formación de metástasis

- Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI15/00447)

- Period: from 2016 to 2018

- Principal investigator: Baulida Estadella, Josep

• Implicaciones clínicas de la expresión de Galectina-1 en cáncer genitourinario: su papel en el diagnóstico, pronóstico, y en la predicción a la respuesta con inhibidores de los “check-point” inmunes

- Financing institution: Asociación Española Contra el Cáncer Catalunya

- Period: from 2016 to 2018

- Principal investigator: Navarro Medrano, Pilar

• Nuevas funciones de Galectina-1 y CPEBs en cáncer: papel en la remodelación del estroma tumoral, invasión/metástasis y pluripotencialidad celular. Implicaciones clínicas

- Financing institution: Fondo de Investigación Sanitaria. ISCIII (PI14/00125)

- Period: from 2015 to 2019

- Principal investigator: Navarro Medrano, Pilar

 

Group’s Recognitions

• Officially recognised as a consolidated research group by the Generalitat de Catalunya: Grup de Recerca en Transició Epiteli-Mesènquima i Invasió Tumoral. 2017 to 2020

- Agència de Gestió d'Ajuts Universitaris i de Recerca (SGR 24)

- Principal investigator: García de Herreros Madueño, Antonio

• Officially recognised as a consolidated research group by the Generalitat de Catalunya: Cellular and molecular mechanisms of disease. 2017 to 2020

- Agència de Gestió d'Ajuts Universitaris i de Recerca (SGR 225)

- Principal investigator: Navarro Medrano, Pilar

 

Theses

• Sala-Romanyà L. Methyltransferase inhibitors interfere with Snail1 action on myofibroblast activity to prevent fibrosis and metastasis. Universitat Pompeu Fabra.

- Director: Baulida Estadella, Josep

- Date of defense: 20/06/2018

• Genovès J. Evolució de les lesions CIN-2 segons la P16 i el Ki-67. Universitat Autònoma de Barcelona.

- Directors: Mancebo Moreno, Gemma; Carreras Collado, Ramon; Alameda Quitllet, Francesc

- Date of defense: 08/11/2018

 

 

 

 

 

 

 

 

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