RECERCA TRANSLACIONAL
Grup d’expressió gènica i càncer

JOAN SEOANE

JOAN SEOANE
Investigador Principal
Biosketch

OBJECTIUS ESTRATÈGICS

  • Identificar agents terapèutics contra tumors cerebrals i també identificar biomarcadors nous per predir respostes a teràpies.

OBJECTIUS ACTUALS

  • Estudi de l’heterogeneïtat intratumoral.
  • Aconseguir una millor comprensió dels mecanismes moleculars implicats en les cèl·lules d’iniciació del càncer/mare cèl·lules.
  • Desenvolupar mètodes per al diagnòstic molecular no invasiu a través de l’estudi de biomarcadors circulants.
  • Generar models de tumors cerebrals en ratolí derivats de pacients.

COMPONENTS

Gene Expression & Cancer Group
  • Investigador Principal
    • Joan Seoane
  • Becarios Post-Doctorales
    • Raffaella Iurlaro
    • Regina Mayor
    • Josep Lluís Parra
    • Mónica Pascual
  • Estudiant llicenciat
    • Ester Arroba
  • Tècnics
    • Alexandra Arias Piñeiro
    • Isabel Cuartas Maza
    • Carolina Raventós Bernal
    • Cristina Sánchez

EN LES NOTÍCIES


Publicacions científiques més rellevants

  • Gueorguieva I, Cleverly A, Desaiah D, Azaro A, Seoane J, Braña I, Sicart E, Miles C, Lahn MM, Mitchell MI, Rodon J. Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.  Drugs Context. 2016 Dec 2;5:212303. eCollection 2016.
  • Seoane J. The Taming of the TAMs. Trends Cell Biol. 2016 Aug;26(8):562-3.
  • De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J*. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nature Communications. 2015; 6:8839. (*corresponding author).
  • Rodon L, Gonzalez-Junca A, Inda MD, Sala-Hojman A, Martinez-Saez E, Seoane J*. Active CREB1 promotes a malignant TGF-β2 autocrine loop in glioblastoma. Cancer Discov. 2014; 4(10):1230-41. (*corresponding author).
  • Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratu G, Parra JL, De Mattos-Arruda L, Grueso J, Hernandez-Losa J, Arribas J, Prudkin L, Nuciforo P, Scaltriti M, Seoane J*, Baselga J*. Clinical response to a lapatinib-based therapy of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation. Cancer Discov. 2013; 3(11):1238-44 (*co-corresponding authors).
  • Eichhorn PJ, Rodon L, Gonzàlez-Juncà A, Dirac A, Gili M, Martínez-Sáez E, Aura C, Barba I, Peg V., Prat A., Cuartas I, Jimenez J, García-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane J. USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma. Nature Medicine 2012;18(3):429-35. [see News and Views: Aggarwal K and Massagué J. Ubiquitin removal in the TGF- β pathway. Nature Cell Biology. 2012;14(7):656-7].
  • Anido J, Sáez-Borderías A, Gonzàlez-Juncà A, Rodón L, Folch G, Carmona MA, Prieto-Sánchez RM, Barba I, Martínez-Sáez E, Prudkin L, Cuartas I, Raventós C, Martínez-Ricarte F, Poca MA, García-Dorado D, Lahn M, Yingling J, Rodón J, Sahuquillo J, Baselga J, Seoane J. TGF-β receptor inhibitors target the CD44high/Id1high glioma-initiating cell population in human glioblastoma. Cancer Cell. 2010;18(6):655-68 [see Preview: Edwards LA, Fine HA. The Ids have it. Cancer Cell. 2010;18(6):543-5.

Totes les publicacions

  • Gueorguieva I, Cleverly A, Desaiah D, Azaro A, Seoane J, Braña I, Sicart E, Miles C, Lahn MM, Mitchell MI, Rodon J. Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.  Drugs Context. 2016 Dec 2;5:212303. eCollection 2016.
  • Seoane J. The Taming of the TAMs. Trends Cell Biol. 2016 Aug;26(8):562-3.
  • Gomis R, Seoane J. TGFβ Family Signaling in Tumor Suppression and Cancer Progression. Cold Harbor 2016. In press 2016
  • Byrne A, Alferez D, Amant F, Annibali D, Arribas J, Biankin A, Bruna A, Budinská E, Caldas C, Chang D, Clarke R, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek M, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer H, Peeper D, Pelicci PG, Piris A, Roman-Roman S, Rueda O, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in oncology and cancer precision medicine using Patient-Derived Xenograft models. Nature Review Cancer. In Press 2016
  • Gueorguieva I, Cleverly A, Desaiah D, Azaro A, Seoane J, Braña I, et al. Drugs in Context 2016; 5:201303. “Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer”, Drugs in Context, 2016; 5: 201303. DOI: 10.7573/dic.212303
  • Seoane J. The Taming of the TAMs. Trends in Cell Biology. Aug;26(8):562-3. doi: 10.1016/j.tcb.2016.06.007. Epub 2016 Jul 6.
  • De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J*. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nature Communications. 2015; 6:8839. (*corresponding author).
  • De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, Losurdo A, Pérez-Garcia J, Masci G, Corsi F, Cortés J, Seoane J, Calin GA, Santarpia L. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget. 2015;6(35):37269-80.
  • Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG 2nd, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015;5(11):1164-77
  • Iyengar PV, Jaynes P, Rodon L, Lama D, Law KP, Lim YP, Verma C, Seoane J, Eichhorn PJ. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Sci Rep. 2015;5:14733.
  • Ulloa F, Gonzàlez-Juncà A, Meffre D, Barrecheguren PJ, Martínez-Mármol R, Pazos I, Olivé N, Cotrufo T, Seoane J, Soriano E. Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth. PLoS One. 2015;10(3):e0119707.
  • Rodon J, Carducci MA, Sepulveda-Sanchez JM, Azaro A, Calvo E, Seoane J, Brana I, Sicart E, Gueorguieva I, Cleverly AL, Sokalingum Pillay N, Desaiah D, Estrem ST, Paz-Ares L, Holdoff M, Blakeley J, Lahn MM, Baselga J. First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma. Clin Cancer Res. 2015;21(3):553-60.
  • Rodon J, Carducci M, Sepulveda-Sánchez JM, Azaro A, Calvo E, Seoane J, Braña I, Sicart E, Gueorguieva I, Cleverly A, Pillay NS, Desaiah D, Estrem ST, Paz-Ares L, Holdhoff M, Blakeley J, Lahn MM, Baselga J. Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-β receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer. Invest New Drugs. 2015;33(2):357-70.
  • Seoane J*, De Mattos-Arruda L. Escaping out of the brain. Cancer Discov. 2014;4(11):1259-61. (*corresponding author)
  • Hidalgo M, Amant F, Biankin AV, Budinská E, Byrne AT, Caldas C, Clarke RB, de Jong S, Jonkers J, Mælandsmo GM, Roman-Roman S, Seoane J, Trusolino L, Villanueva A. Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research. Cancer Discov. 2014;4(9):998-1013.
  • Henderson D, Ogilvie LA, Hoyle N, Keilholz U, Lange B, Lehrach H on behalf of the OncoTrack Consortium. Personalized medicine approaches for colon cancer driven by genomics and systems biology: OncoTrack. Biotechnol J. 2014;9(9):1104-14.
  • Rodon L, Gonzalez-Junca A, Inda MD, Sala-Hojman A, Martinez-Saez E, Seoane J*. Active CREB1 promotes a malignant TGF-β2 autocrine loop in glioblastoma. Cancer Discov. 2014;4(10):1230-41. (*corresponding author)
  • Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, Folch G, Gonzalez-Juncà A, Sodir NM, Masso-Vallés D, Beaulieu ME, Swigart LB, Mc Gee MM, Somma MP, Nasi S, Seoane J, Evan GI, Soucek L. Myc inhibition is effective against glioma and reveals a role for Myc in mitosis. Nature Communications. 2014;5:4632.
  • De Mattos-Arruda L, Weigelt B, Cortes J, Won HH, Ng CK, Nuciforo P, Bidard FC, Aura C, Saura C, Peg V, Piscuoglio S, Oliveira M, Smolders Y, Patel P, Norton L, Tabernero J, Berger MF, Seoane J, Reis-Filho JS. Capturing Intra-Tumor Genetic Heterogeneity by De Novo Mutation Profiling of Circulating Cell-Free Tumor DNA: A Proof-of-Principle. Ann Oncol. 2014;25(9):1729-35.
  • Martino-Echarri E, Fernández-Rodríguez R, Bech-Serra JJ, Plaza-Calonge MC, Vidal N, Casal C, Colomé N, Seoane J*, Canals F, Rodríguez-Manzaneque JC. Relevance of IGFBP2 proteolysis in glioma and contribution of the extracellular protease ADAMTS1. Oncotarget. 2014;5(12):4295-304. (*corresponding author)
  • Seoane J. Gremlins Sabotage the Mechanisms of Cancer Stem Cell Differentiation. Cancer Cell. 2014;25(6):716-7.
  • Seoane J*, De Mattos-Arruda L. Brain metastasis: new opportunities to tackle therapeutic resistance. Review Article, Mol Oncol. 2014;8(6):1120-31. (*corresponding author).
  • Seoane J*, De Mattos-Arruda L. The challenge of intratumour heterogeneity in precision medicine. J Intern Med. 2014;276(1):41-51. (*corresponding author)
  • Inda MD, Bonavia R, Seoane J*. Glioblastoma multiforme: a look inside its heterogeneous nature. Cancers (Basel). 2014;6(1):226-39. (*co-corresponding author).
  • Cortés J, Calvo E, Vivancos A, Perez-Garcia J, Recio JA, Seoane J. New approach to cancer therapy based on a molecularly defined cancer classification. CA-Cancer J Clin. 2014;64(1):70-4.
  • De Mattos-Arruda L, Bidard FC, Won HH, Cortes J, Ng CK, Peg V, Nuciforo P, Jungbluth AA, Weigelt B, Berger MF, Seoane J*, Reis-Filho JS. Establishing the origin of metastatic deposits in the setting of multiple primary malignancies: The role of massively parallel sequencing. Mol Oncol. 2014;8(1):150-8 (*co-corresponding authors).
  • Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratu G, Parra JL, De Mattos-Arruda L, Grueso J, Hernandez-Losa J, Arribas J, Prudkin L, Nuciforo P, Scaltriti M, Seoane J*, Baselga J*.Clinical response to a lapatinib-based therapy of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation. Cancer Discov. 2013;3(11):1238-44 (*co-corresponding authors).
  • De Mattos-Arruda L, Cortes J, Santarpia L, Vivancos A, Tabernero J, Reis-Filho JS, Seoane J. Circulating Tumor Cells and Cell-Free DNA as Tools for Managing Breast Cancer. Nature Reviews. Clinical Oncology. 2013;10(7):377-89.
  • De Mattos-Arruda L, Tabernero J, Seoane J, Cortes J. Circulating tumour cells in early breast cancer. Lancet Oncol. 2012;13(9):e370.
  • Ros-Blanco L, Anido J, Bosser R, Este J, Clotet B, Kosoy A, Ruiz-Avila L, Teixido J, Seoane J*, Borrell JI. NonCyclam Tetraamines inhibit CXC Chemokine Receptor Type 4 and target Glioma-Initiating Cells. J Med Chem. 2012;55(17):7560-70 (*co-corresponding author).
  • Eichhorn PJ, Rodon L, Gonzàlez-Juncà A, Dirac A, Gili M, Martínez-Sáez E, Aura C, Barba I, Peg V., Prat A., Cuartas I, Jimenez J, García-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane J. USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma. Nature Medicine 2012;18(3):429-35. [see News and Views: Aggarwal K and Massagué J. Ubiquitin removal in the TGF- β pathway. Nature Cell Biology. 2012;14(7):656-7].
  • Anido J, Sáez-Borderías A, Gonzàlez-Juncà A, Rodón L, Folch G, Carmona MA, Prieto-Sánchez RM, Barba I, Martínez-Sáez E, Prudkin L, Cuartas I, Raventós C, Martínez-Ricarte F, Poca MA, García-Dorado D, Lahn M, Yingling J, Rodón J, Sahuquillo J, Baselga J, Seoane J. TGF-β receptor inhibitors target the CD44high/Id1high glioma-initiating cell population in human glioblastoma. Cancer Cell. 2010;18(6):655-68 [see Preview: Edwards LA, Fine HA. The Ids have it. Cancer Cell. 2010;18(6):543-5.
  • Seoane J. NO Signals from the Cancer Stem Cell Niche. Cell Stem Cell. 2010;6(2):97-8.
  • Seoane J. TGF-β and cancer initiating cells. Cell Cycle. 2009;8(23):3787-8.
  • Santamaria-Martínez A, Barquinero J, Barbosa-Desongles A, Hurtado A, Pinós T, Seoane J, Poupon MF, Morote J, Reventós J, Munell F. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis. Exp Cell Res. 2009 ;315(17):3004-13.
  • Peñuelas S, Anido J, Prieto-Sánchez RM, Folch G, Barba I, Cuartas I, García-Dorado D, Poca MA, Sahuquillo J, Baselga J, Seoane J. TGF-β increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell. 2009;15(4):315-27 [see Preview: Fine HA. Glioma stem cells: not all created equal. Cancer Cell. 2009;15(4):247-9].
  • Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, Baselga J. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3- kinase inhibitor NVP-BEZ235. Cancer Res. 2008;68(22):9221-30.
  • Seoane J. The TGF-β pathway as a therapeutic target in cancer. Clin Transl Oncol. 2008;10(1):14-19.
  • Baselga J, Rothenberg ML, Tabernero J, Seoane J, Daly T, Cleverly A, Berry B, Rhoades SK, Ray CA, Fill J, Farrington DL, Anne L, Yingling JM, Lahn M, Arteaga C, Carducci M. TGF-β signaling related markers in cancer patients with bone metastasis. Biomarkers. 2008;13(2):217-36.
  • Seoane J. TGF-β signaling in homeostasis and cancer. In: Jakowlew SB (ed.) Cancer Drug Discovery and Development: Transforming Growth Factor-Beta in Cancer Therapy, Vol. 1: Basic and Clinical Biology . 1st ed. Totowa, NJ: Humana Press; 2008. pp 23-35.
  • Bruna A, Darken RS, Rojo F, Ocaña A, Peñuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J, Seoane J. High TGF-β-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 2007;11,147-160 [see Preview: Kesari S, Jackson-Grusby L, Stiles CD. “Smad”eningly erratic: target gene methylation determines whether TGFbeta promotes or suppresses malignant glioma. Dev Cell. 2007;12(3):324-5.].
  • Gomis RR, Alarcón C, He W, Wang Q, Seoane J, Lash A and Massagué J. A FoxO-Smad synexpression group in human keratinocytes. P Natl Acad Sci USA. 2006;103(34):12747-52.
  • Seoane J. Escaping from the TGF-β anti-proliferative control. Carcinogenesis. 2006;27(11):2148-56.
  • Massagué J, Seoane J, Wotton D. Smad Transcription Factors. Gene Dev. 2005;19,2783-2810.
  • Seoane J, Le H-V, Shen L, Anderson SA, Massagué J. Integration of Smad and Forkhead Pathways in the Control of Neuroepithelial and Glioblastoma Cell Proliferation. Cell. 2004;117,211-223 (Cover) [see Preview: Arden KC. FoxO: Linking new signaling pathways. Mol Cell. 2004;14(4):416-8].
  • Seoane J. p21(WAF1/CIP1) at the Switch Between the Anti-Oncogenic and Oncogenic Faces of TGF-β. Cancer Biol Ther. 2004;3(2):226-7.
  • Calonge J, Seoane J, Massagué J. Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-β. J Biol Chem. 2004;279(22):23759-65.
  • Seoane J, Le H-V, Massagué J. Myc suppression of p21Cip1 Cdk inhibitor determines the outcome of the p53 response to DNA damage. Nature. 2002;419(6908):729-34 [see Preview: Vousden KH. Switching from life to death: the Miz-ing link between Myc and p53. Cancer Cell. 2002;2(5):351-2].
  • Wu J-W, Hu M, Chai J, Seoane J, Huse M, Li C, Kyin S, Fairman R, Muir TW, Massague J, Shi Y. Crystal structure of a phosphorylated Smad2: Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-β signaling. Mol Cell. 2001;8(6):1277-89.
  • Seoane J, Pouponnot C, Staller P, Schader M, Eilers M, Massagué J. TGF-β influences Myc, Miz-1 and Smad to control the CDK inhibitor p15Ink4b. Nature Cell Biology. 2001;3(4):400-8.
  • Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massagué J, Hanel F, Eilers M. Repression of p15Ink4b expression by Myc through association with Miz-1. Nature Cell Biology. 2001;3,392-399.
  • Hata A, Seoane J, Lagna G, Montalvo E, Hemmati-Brivanlou A, Massagué J.  OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell. 2000;100(2):229-40.
  • De la Iglesia N, Mukhtar M, Seoane J, Guinovart JJ, Agius L. The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. J Biol Chem. 2000;275(14):10597-603.
  • Warner BJ, Blain SW, Seoane J, Massagué J. Myc downregulation by transforming growth factor beta required for activation of the p15 Ink4b G1 arrest pathway. Mol Cell Biol. 1999;19(9):5913-22.
  • Seoane J, Barberà A, Telemaque-Potts S, Newgard SB, Guinovart JJ. Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male zucker diabetic fatty rats. J Biol Chem. 1999;274(45):31833-8.
  • Seoane J, Trinh K, O’Doherty RM, Gómez-Foix AM, Lange AJ, Newgard CB, Guinovart JJ. Metabolic impact of adenovirus-mediated overexpression of the glucose 6-phosphatase catalytic subunit in hepatocytes. J Biol Chem. 1997;272(43):26972-7.
  • Guinovart JJ, Gómez-Foix AM, Seoane J, Fernández-Novell JM, Bellido D, Vilaró S. Bridging the gap between glucose phosphorylation and glycogen synthesis in the liver. Biochem Soc T. 1997;25(1):157-60.
  • Seoane J, Gómez-Foix AM, O´Doherty RM, Gómez-Ara C, Newgard CB, Guinovart JJ. Glucose 6-phosphate produced by glucokinase, but not hexokinase I, promotes the activation of hepatic glycogen synthase. J Biol Chem. 1996;271(39):23756-60.
  • O’Doherty RM, Lehman DL, Seoane J, Gómez-Foix AM, Guinovart JJ, Newgard CB. Differential metabolic effects of adenovirus-mediated glucokinase and hexokinase I overexpression in rat primary hepatocytes. J Biol Chem. 1996;271(34):20524-30.