Rosa Farràs
TEL: +34 963289681 Ext. 2208
FAX: +34 963289701

Jose Miguel Pardo Sanchez

Pre-Doctoral Researcher
Arantxa Martinez Ferriz

Laboratory technician
Carolina Gandia Ventura

Oncogenic Signalling

We are interested in the characterization of the signal transduction pathways and protein post-translational modifications controlling the regulation of gene transcription and protein turnover. This is a critical area of cancer research, since accelerated cell growth and dysregulated protein turnover is a major feature of tumour formation and progression. Our projects employ state-of-the-art biochemistry, molecular and cell biology and genetics to characterize the basis of the regulation of these fundamental processes:

  1. Signalling networks in lung cancer stem cells. Lung cancer is the most common cause of cancer-related death worldwide. The acquisition of resistance to treatment is one of the main reasons of its high mortality. The resistance to treatment and metastasis can be related to the presence of cancer stem cells (CSCs), since these cells, with the capacity to self-renew, differentiate, initiate and maintain tumour growth, are resistant to conventional chemotherapy. Therefore, the CSCs are a promising therapeutic target with great potential. We are currently working on the identification and isolation of human tumour-derived CSCs from both biological samples from resectable non-small cell lung cancer (NSCLC) patients and immortalized cell lines, with the aim to analyze both the phospho-proteome and the transcriptome to reveal oncogenic signalling pathways activated in these cells. The results obtained will be used for the design of rational therapeutic strategies that may be effective on the CSCs carrying different mutations through the use of inhibitors/modulators of oncogene signalling pathways.
  2. Regulation of AP-1 transcription factor by oncogenic pathways. AP-1 transcription factors are crucial molecules for integrating intra-and extracellular signals, and their activity is regulated by a series of post-translational modifications. AP-1 is also involved in various pathologies, including leukaemia and lymphoma in which AP-1 proteins are often dysregulated. In this context, we are investigating the molecular mechanisms by which dysregulation of JunB, a member of the AP-1 transcription factor family, alter gene expression to allow adaptation of the cancer cells to their environment. In addition to studies of ubiquitylation and proteasomal degradation of JunB, we are also pursuing the characterization of its bona fide genomic targets combining large-scale genomic and transcriptomic approaches with functional studies.

Selected Publications

mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.
Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, Fernandez-Ruiz S, Sutherland JD, Clasquin M, Tomas-Cortazar J, Jimenez J, Torres I, Quang P, Ximenez-Embun P, Bago R, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Torrano V, Cabrera D, van Liempd SM, Cendon Y, Castro E, Murray S, Revandkar A, Alimonti A, Zhang Y, Barnett A, Lein G, Pirman D, Cortazar AR, Arreal L, Prudkin L, Astobiza I, Valcarcel-Jimenez L, Zuñiga-García P, Fernandez-Dominguez I, Piva M, Caro-Maldonado A, Sánchez-Mosquera P, Castillo-Martín M, Serra V, Beraza N, Gentilella A, Thomas G, Azkargorta M, Elortza F, Farràs R, Olmos D, Efeyan A, Anguita J, Muñoz J, Falcón-Pérez JM, Barrio R, Macarulla T, Mato JM, Martinez-Chantar ML, Cordon-Cardo C, Aransay AM, Marks K, Baselga J, Tabernero J, Nuciforo P, Manning BD, Marjon K, Carracedo A
Nature , 2017 Jul 6, vol. 547, pag. 109-113
Quantitation of Protein Translation Rate In Vivo with Bioorthogonal Click-Chemistry.
Belda-Palazón B, Ferrando A, Farràs R
Methods in molecular biology (Clifton, N.J.) , 2016, vol. 1449, pag. 369-82
Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells.
Soto-Cerrato V, Manuel-Manresa P, Hernando E, Calabuig-Fariñas S, Martínez-Romero A, Fernández-Dueñas V, Sahlholm K, Knöpfel T, García-Valverde M, Rodilla AM, Jantus-Lewintre E, Farràs R, Ciruela F, Pérez-Tomás R, Quesada R
Journal of the American Chemical Society , 2015 Dec 23, vol. 137, pag. 15892-8
GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase.
Pérez-Benavente B, García JL, Rodríguez MS, Pineda-Lucena A, Piechaczyk M, Font de Mora J, Farràs R
Oncogene , 2013 Apr 25, vol. 32, pag. 2189-99
JunB breakdown in mid-/late G2 is required for down-regulation of cyclin A2 levels and proper mitosis.
Farràs R, Baldin V, Gallach S, Acquaviva C, Bossis G, Jariel-Encontre I, Piechaczyk M
Molecular and cellular biology , 2008 Jun, vol. 28, pag. 4173-87