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Contact

Dr. Piero Crespo


Phone: (+34) 942 200959 / Fax : (+34) 942 266399
Email: crespop@unican.es

Mailing address: IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander


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GRUPO FINANCIADO POR LA RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA EN CÁNCER DEL ISCIII/FEDER (RD12/0036/0033). 2012-2016
Grupo incluído en el programa: Molecular Mechanisms in Cancer. Involucrado en el desarrollo de nuevas estratégias terapéuticas para inhibir rutas de señalización pro-tumorales.


Spatial regulation of Ras-ERK signals in cancer

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Principal Investigator

Dr. Piero Crespo, Full Professor (CSIC)


Other personnel

  • Lorena Agudo Ibáñez, postdoctoral
  • Berta Casar Martínez, postdoctoral
  • Ana Herrero Mier, postdoctoral
  • Vincenzo Cappitelli, predoctoral
  • Dalia de la Fuente Vivas, predoctoral
  • Rocío García Gómez, predoctoral
  • Yaiza García Ibáñez, predoctoral
  • Ana Martín Vega, predoctoral
  • Marta Morante Ezquerra, predoctoral
  • Alicia Noriega Tato, lab. technician


Research lines

  • Spatial regulation of Ras-ERK signals in physiological processes and in cancer

  • Development of antitumoral drugs targeting protein-protein interactions in the Ras-ERK pathway


Funding

  • "Las interacciones entre proteínas scaffolds y dímeros de ERK como dianas antitumorales". BFU2011-23807. 2012-2015.
  • “Nuevas dianas moleculares en la ruta Ras-ERK: potencial terapéutico en el cáncer de tiroides”. Asociación Española Contra el Cáncer (AECC). GCB141423113. Proyecto coordinado 2014-2019.
  • Red Temática de Investigación Cooperativa sobre el Cáncer (RTICC). RD/12/0036/0033. 2012-2015.
  • “Proteínas Scaffold como moduladores de la resistencia a inhibidores de la ruta RAS-ERK en melanoma”.  SAF-2015 63638R.  2016-2018.


Relevant publications (last 10 years)

  • Santos E, Crespo P. The RAS-ERK pathway: A route for couples.
    Sci Signal
    . 2018 Oct 30;11(554). pii: eaav0917. doi: 10.1126/scisignal.aav0917. [PubMed]

  • Casar B, Badrock AP, Jiménez I, Arozarena I, Colón-Bolea P, Lorenzo-Martín LF, Barinaga-Rementería I, Barriuso J, Cappitelli V, Donoghue DJ, Bustelo XR, Hurlstone A, Crespo P. RAS at the Golgi antagonizes malignant transformation through PTPRκ-mediated inhibition of ERK activation.
    Nat Commun
    . 2018 Sep 5;9(1):3595. doi: 10.1038/s41467-018-05941-8. [PubMed]

  • García-Gómez R, Bustelo XR, Crespo P. Protein-Protein Interactions: Emerging Oncotargets in the RAS-ERK Pathway

    Trends Cancer. 2018 Sep;4(9):616-633. doi: 10.1016/j.trecan.2018.07.002. Epub 2018 Aug 9. [PubMed]
  • Agudo-Ibáñez L, Herrero A, Barbacid M, Crespo P. Correction for Agudo-Ibáñez et al., "H-Ras Distribution and Signaling in Plasma Membrane Microdomains Are Regulated by Acylation and Deacylation Events".
    Mol Cell Biol
    . 2018 Aug 15;38(17). pii: e00335-18. doi: 10.1128/MCB.00335-18. Print 2018 Sep 1. [PubMed]

  • Crespo P., and Casar B. The chick embryo chorioallantoic membrane as an in vivo model to study metastasis.
    Bio-protocol,
    http://bio-protocol.org/e1962. (2016)
  • Casar B, Crespo P. ERK Signals: Scaffolding Scaffolds?
    Front Cell Dev Biol. 2016 May 31; 4:49. [PubMed]

  • Herrero A, Casar B, Colón-Bolea P, Agudo-Ibáñez L, Crespo P. Defined spatiotemporal features of RAS-ERK signals dictate cell fate in MCF-7 mammary epithelial cells.
    Mol Biol Cell
    . 2016 Apr 20. [Epub ahead of print][PubMed]

  • Herrero A, Crespo P. Tumors topple when ERKs uncouple.
    Mol Cell Oncol
    . 2015 Oct 29;3(2):e1091875. eCollection 2016 Mar. [PubMed]

  • Muñoz-Félix JM, Fuentes-Calvo I, Cuesta C, Eleno N, Crespo P, López-Novoa JM, Martínez-Salgado C. Absence of K-Ras Reduces Proliferation and Migration But Increases Extracellular Matrix Synthesis in Fibroblasts.
    J Cell Physiol
    . 2016 Feb 12. [Epub ahead of print][PubMed]

  • Herrero A, Pinto A, Colón-Bolea P, Casar B, Jones M, Agudo-Ibáñez L, Vidal R, Tenbaum SP, Nuciforo P, Valdizán EM, Horvath Z, Orfi L, Pineda-Lucena A, Bony E, Keri G, Rivas G, Pazos A, Gozalbes R, Palmer HG, Hurlstone A, Crespo P. Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.
    Cancer Cell
    . 2015 Aug 10;28(2):170-82. [PubMed]

  • Agudo-Ibáñez L, Herrero A, Barbacid M, Crespo P. H-Ras distribution and signaling in plasma-membrane microdomains are regulated by acylation and deacylation events. Agudo-Ibáñez L, Herrero A, Barbacid M, Crespo P.
    Mol Cell Biol
    . 2015 Mar 16. [PubMed]

  • Colón-Bolea P, Crespo P. Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK pathway.
    Bioessays
    . 2014 Dec;36(12):1162-9. [PubMed]

  • Baschieri F, Confalonieri S, Bertalot G, Di Fiore PP, Dietmaier W, Leist M, Crespo P, Macara IG, Farhan H. Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis.
    Nat Commun
    . 2014 Sep 11;5:4839. [PubMed]
  • Fuentes-Calvo I, Crespo P, Santos E, López-Novoa JM, Martínez-Salgado C. The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation and migration in fibroblasts.
    Biochim Biophys Acta
    . 2013 Dec;1833(12):2734-44. [PubMed]
  • Matallanas D, Romano D, Al-Mulla F, O'Neill E, Al-Ali W, Crespo P, Doyle B, Nixon C, Sansom O, Drosten M, Barbacid M, Kolch W. Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.
    Mol Cell
    . 2011 Dec 23;44(6):893-906. [PubMed]
  • Crespo P, Calvo F, Sanz-Moreno V. Ras and Rho GTPases on the move: The RasGRF connection.
    Bioarchitecture
    . 2011 Jul;1(4):200-204. [PubMed]
  • Rodríguez J, Crespo P. Working without kinase activity: phosphotransfer-independent functions of extracellular signal-regulated kinases.
    Sci Signal
    . 2011 Oct 25;4(196):re3. [PubMed]
  • Casar B., Rodríguez J., Gibor G., Seger R., and Crespo P. "Mxi2 sustains ERK1/2 phosphorylation levels in the nucleus by preventing ERK1/2 binding to phosphatases".
    Biochem. J., 441, 571-578. (2012).
  • Matallanas D., Romano D., Al-Mulla F., O'Neil E., Al-Ali W, Crespo P., Doyle B, Nixon B, Samson O, Drosten M., Barbacid M., and Kolch W. "K-Ras oncogene addiction requires the presence of the wildtype allele, EGF signalling and shutdown of MST2 signalling".
    Mol. Cell, 44, 893-906. (2011).
  • Calvo F., Sanz-Moreno V, Agudo-Ibáñez L., Wallberg F., Sahai E., Marshall C.J., and Crespo P. "Ras GEFs as inhibitors of Rho GTPases: RasGRF suppresses Cdc42-mediated tumor cell movement, cytoskeletal dynamics and transformation".
    Nat. Cell Biol. 13, 819-826. (2011). (Seleccionado por The Faculty of 1000).
  • Arozarena I., Calvo F., Agudo-Ibañez L. and Crespo P. "An actor on many stages: Ras subcellular localization, site-specific regulation and functions".
    Genes & Cancer. 182-194. (2011).
  • Matallanas D., and Crespo P. "New druggable targets in the Ras pathway?
    Curr. Opin. Mol. Ther. 12, 674-683. (2010).
  • Rodríguez J., Calvo F., González J.M., Casar B., Andrés V. and Crespo P., "ERK1/2 MAP kinases promote cell cycle entry by rapid, kinase-independent disruption of Retinoblastoma–LaminA complexes".
    J. Cell Biol. 191, 967-979. (2010). (Editorial en el mismo número; Editorial en Science Sig. 3, ec371 2010; Seleccionado por The Faculty of 1000).
  • Chiariello M., Vaqué J.P., Crespo P., and Gutkind J.S. "Activation of Ras and Rho GTPases and MAP kinases by G-Protein-coupled receptors". Meths. Mol. Biol. 661, 137-150. (2010).
  • Pinto A. and Crespo P. "Analysis of ERKs dimerization by electrophoresis".
    Meths. Mol. Biol. 661, 335-342. (2010).
  • Calvo F., Agudo-Ibáñez L., and Crespo P. "The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumour therapies".
    Bioessays. 32, 412-421. (2010).
  • Calvo F., and Crespo P. "Structural and spatial determinants regulating TC-21 activation by RasGRF family Nucleotide Exchange Factors".
    Mol. Biol. Cell, 20, 4289-4302. (2009).
  • Casar B., Pinto A., and Crespo P. "ERK dimers and scaffold proteins: unexpected partners for a forgotten (cytoplasmic) task".
    Cell Cycle, 8, 1007-1013. (2009).
  • Casar B., Arozarena I., Sanz-Moreno V., Pinto A., Agudo-Ibáñez L., Marais R., Lewis R.E., Berciano M.T. and Crespo P. "Ras subcellular localization defines ERKs substrate specificity though distinct utilization of scaffold proteins".
    Mol. Cell. Biol., 29, 1338-1353. (2009). (Seleccionado por The Faculty of 1000).
  • González J.M., Navarro A., Casar B., Crespo P., and Andrés V. "Fast regulation of AP-1 activity through interaction of lamin A/C, ERK 1/2 and c-Fos at the nuclear envelope".
    J. Cell Biol., 183, 653-666. (2008). (Seleccionado por The Faculty of 1000).
  • Casar B., Pinto A., and Crespo P. "Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes".
    Mol. Cell, 31, 708-721. (2008). (Seleccionado por The Faculty of 1000; Editorial en Science Sig. 1, ec315 2008).
  • Vaqué J.P., Fernández-García B., García P., Calvo F., Crespo P, Marín M.C. and León J., "c-Myc inhibits Ras-mediated differentiation of neuroendocrine cells by blocking c-Jun up-regulation".
    Mol. Cancer Res., 6, 325-339. (2008).
  • Agudo-Ibáñez L., Núñez F., Calvo F., Berenjeno I.M, Bustelo X.R., and Crespo P. "Transcriptomal profiling of site-specific Ras signals".
    Cell. Signal., 19, 2264-2276. (2007).
  • Martínez S.E., Lázaro-Diéguez F., Selva J., Calvo F., Renau-Piquéras J., Crespo P., Claro E., and Egea G. "Lysophosphatidic acid rescues Rho A activation and phosphoinositide levels in astrocytes exposed to ethanol".
    J. Neurochem., 102, 1044-1052. (2007).
  • Casar B., Sanz-Moreno V., Yazicioglu M.N., Rodríguez J., Berciano M.T., Lafarga M., Cobb M.H., and Crespo P. "Mxi2 promotes stimulus-independent ERK nuclear translocation".
    EMBO J., 26, 635-646. (2007). (Seleccionado por The Faculty of 1000).
  • Peregrín S., Jurado M, Sanz-Moreno V, Ruiz-Gómez A, Crespo P., Mayor, jr F. and Murga C. "Phosphorylation of p38 by GRK2 at the docking groove unveils a novel mechanism for inactivating p38 MAPK".
    Curr. Biol., 16, 2042-2047. (2006). (Seleccionado por The Faculty of 1000).
  • Matallanas D., Sanz-Moreno V., Arozarena I., Calvo F., Agudo-Ibáñez L., Santos E., Berciano M.T., and Crespo P. "Distinct utilization of effectors and biological outcomes resulting from site-specific Ras activation: Ras functions in lipid rafts and Golgi complex are dispensable for proliferation and transformation".
    Mol. Cell. Biol., 26, 100-116. (2006).