CFAH GENE EXPRESSION AND CANCER GROUP – VHIO – Vall d'Hebron Institute of Oncology

GENE EXPRESSION AND CANCER GROUP

PRECLINICAL & TRANSLATIONAL RESEARCH
Gene Expression and Cancer Group

JOAN SEOANE
Principal Investigator
Biosketch

We study primary brain tumors and brain metastasis; some of the most aggressive of all cancers. Both glioblastoma and brain metastasis are dismal diseases with limited therapeutic options. Advancing progress in this field towards improving outcomes for these patients is therefore critical.

Evolving heterogeneity is among one of the major challenges that are currently hampering our efforts aimed at more effectively treating brain cancers. We focus on inter-tumor heterogeneity and evolution that includes genomic heterogeneity, cancer initiating cells and stroma/immune cell heterogeneity – including the study of TGF-β and LIF.

Tumors are composed of a mosaic of cell subclones that differ in their genomic alterations. Our group explores the genomic diversity present in glioblastoma and analyzes intratumor genomic heterogeneity as it evolves over time in response to therapy. We are designing tools to monitor evolving genomic heterogeneity, and studying the use of liquid biopsies for brain cancer through the study of circulating cell free tumor DNA in cerebrospinal fluid from patients.

Specifically, we are driving cerebrospinal fluid as liquid biopsy for the real time policing of brain cancer closer to the clinic. Reflective of our expertise in developing this novel approach, we recently first-authored an article (Seoane et al. Ann Oncol. 2019), analyzing several studies on the use of liquid biopsy in primary and metastatic brain tumors for the diagnosis and follow-up of disease as well as the detection of mechanisms of resistance or susceptible mutations.

Building on our previous LIF studies, where we were the first to establish a link between this multi-functional protein and cancer, as well as show that LIF blockade eliminates cancer stem cells and prevents disease progression and recurrence, subsequent research has led to the publication of a further article this year directed by our Group (Pascual-García et al. Nat Commun. 2019.)

We have now shown that the novel agent MSC-1, developed by VHIO, inhibits LIF and has now been shown to have a dual mechanism of action. In tumors expressing high levels of LIF, this protein promotes the proliferation of cancer stem cells. LIF blockade eliminates these tumor-initiating stem cells, putting the brakes on metastatic cell spread and cancer recurrence.

Additionally, elevated LIF expression disables the anti-tumor alarm system and stops the immune system from thwarting cancer’s plans. Blocking LIF reactivates the alarm to call an anti-tumoral immune response.

STRATEGIC GOALS

  • Identify new therapeutic targets against brain tumors and novel biomarkers to more precisely predict response to therapy.
  • Study intratumor heterogeneity.
  • Investigate the tumor microenvironment.
  • Develop methods for non-invasive molecular diagnosis through the study of circulating biomarkers.
  • Generate patient-derived mouse models of brain cancers.

 


HIGHLIGHTS

  • We have successfully translated our discoveries into a clinical trial. Having initiated a first-in-human and first-in-class clinical trial last year with a novel compound, MSC-1 – designed by our group and developed by the VHIO born spin-off, Mosaic Biomedicals, that Joan Seoane founded in 2012 – we have now completed the Phase I study.
  • We continue to develop liquid biopsies based on the analysis of cell free circulating tumor DNA in cerebrospinal fluid for the diagnosis, prognosis and monitoring of patients with brain tumors.
  • Building on our previous research showing the superiority of CSF over plasma, we have embarked on a joint project funded by the Spanish Association against Cancer (AECC). In partnership with colleagues at the Hospital 12 de Octubre(Madrid), and Hospital Clinic de Barcelona, we will develop this concept and determine how it could be implemented in clinical practice.
  • Joan Seoane was awarded by the Ramón Areces Foundation in 2019 to seek out novel immunotherapeutic targets in brain metastases. In multidisciplinary collaboration with Enriqueta Felip, PI of VHIO’s Thoracic Tumors & Head and Neck Cancer Group, and Eva Muñoz, Clinical Investigator of our Breast Cancer & Melanoma Group (PI: Cristina Saura), he will analyze patients’ brain metastases and compare them with respective primary tumors to reveal factors governing clinical response to immune checkpoint blockade

 


TEAM

  • Principal Investigator
    • Joan Seoane
  • Post-Doctoral Fellows
    • Ester Bonfill (CIBERONC)
    • Laura Escudero
    • Raffaella Iurlaro
    • Mónica Pascual (CIBERONC)
    • Ester Planas
    • Carlota Rubio
  • Research Fellow
    • Davide Ciardiello
  • Masters Student
    • Samia Hajem
  • Graduate Student
    • Ester Arroba
  • Technicians
    • Alexandra Arias Piñeiro
    • Isabel Cuartas Maza
    • Alba Martinez

 


Most relevant scientific publications

  • Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, Rubio-Perez C, Iurlaro R, Arias A, Cuartas I, Sala-Hojman A, Escudero E, Martínez-Ricarte F, Huber-Ruano I, Nuciforo P, Pedrosa L, Marques C, Braña I, Garralda E, Vieito M, Squatrito M, Pineda E, Graus F, Espejo C, Sahuquillo J, Tabernero J, Seoane J. LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8 + T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun. 2019 Jun 11;10(1):2416.
  • Martínez-Ricarte F, Mayor R, Martínez-Sáez E, Rubio-Pérez C, Pineda E, Cordero E, Cicuéndez M, Poca MA, López-Bigas N, Ramon y Cajal S, Vieito M, Carles J, Tabernero J, Vivancos A, Gallego S, Graus F, Sahuquillo J, Seoane J. Molecular diagnosis of diffuse gliomas through sequencing of cell-free circulating tumour DNA from cerebrospinal fluid. Clin Cancer Res. 2018 Jun 15;24(12):2812-2819.
  • Capdevila J, Mayor R, Mancuso FF, Iglesias C, Caratù G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Álvarez 4, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J. Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol. 2018 June 1; 29(6): 1454–1460.
  • Seoane J, Capdevila J. The right compound for the right target: tackling RET. Ann Oncol. 2018 Aug 1; 29(8):1623 -1625.
  • Yates LR, Seoane J, Le Tourneau C, Siu LL, Marais R, Michiels S, Soria JC, Campbell P, Normanno N, Scarpa A, Reis-Filho J, Rodon J, Swanton C, Andre F. The European Society of Medical Oncology (ESMO) Precision Medicine Glossary. Ann Oncol. 2018; 29(1):30-35.
  • Seoane J. Division hierarchy leads to cell heterogeneity. Nature. 2017 Sep 14;549(7671):164-166.
  • Huber-Ruano I, Raventos C, Cuartas I, Sánchez-Jaro C, Wosikowski K, Janicot M, Seoane J. An Antisense oligonucleotide targeting TGF-β2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages. Ann Oncol. 2017 Sep 1;28(9):2278-2285
  • Seoane J, Gomis RR. TGFβ Family Signaling in Tumor Suppression and Cancer Progression. Cold Spring Harb Perspect Biol. 2017 Dec 1;9(12).
  • Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinská E, Caldas C, Chang DK, Clarke RB, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek MA, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer HG, Peeper DS, Pelicci PG, Piris-Gimenez A, Roman-Roman S, Rueda OM, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Apr;17(4):254-268.
  • 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.

All publications

  • Pascual-GarcíaM, Bonfill-TeixidorE, Planas-RigolE, Rubio-PerezC, IurlaroR,AriasA, Cuartas I, Sala-HojmanA, Escudero E, Martínez-Ricarte F, Huber-Ruano I, NuciforoP, PedrosaL, MarquesC, BrañaI, GarraldaE, VieitoM, SquatritoM, PinedaE, GrausF, EspejoC, SahuquilloJ, TaberneroJ, SeoaneJ. LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun. 2019 Jun 11;10(1):2416.
  • SeoaneJ, De Mattos-ArrudaL, Le RhunE, BardelliA, WellerM. Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases. Ann Oncol. 2019 Feb 1;30(2):211-218.
  • Siravegna G, Mussolin B, Venesio T, Marsoni S, Seoane J, Dive C, Papadopoulos N, Kopetz S, Corcoran RB, Siu LL, Bardelli A. How liquid biopsies can change clinical practice in oncology. Ann Oncol. 2019 Oct 1;30(10):1580-1590.
  • De Mattos-Arruda L, Sammut SJ, Ross EM, Bashford-Rogers R, Greenstein E, Markus H, Morganella S, Teng Y, Maruvka Y, Pereira B, Rueda OM, Chin SF, Contente-Cuomo T, Mayor R, Arias A, Ali HR, Cope W, Tiezzi D, Dariush A, Dias Amarante T, Reshef D, Ciriaco N, Martinez-Saez E, Peg V, Ramon Y Cajal S, Cortes J, Vassiliou G, Getz G, Nik-Zainal S, Murtaza M, Friedman N, Markowetz F, Seoane J, Caldas C.The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer. Cell Rep. 2019 May 28;27(9):2690-2708.
  • Seoane J. Division hierarchy leads to cell heterogeneity. Nature. 2017 Sep 14;549(7671):164-166.
  • Huber-Ruano I, Raventos C, Cuartas I, Sánchez-Jaro C, Wosikowski K, Janicot M, Seoane J. An Antisense oligonucleotide targeting TGF-β2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages. Ann Oncol. 2017 Sep 1;28(9):2278-2285
  • Seoane J, Gomis RR. TGFβ Family Signaling in Tumor Suppression and Cancer Progression. Cold Spring Harb Perspect Biol. 2017 Dec 1;9(12).
  • Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinská E, Caldas C, Chang DK, Clarke RB, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek MA, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer HG, Peeper DS, Pelicci PG, Piris-Gimenez A, Roman-Roman S, Rueda OM, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Apr;17(4):254-268.
  • 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.