Grupo de Transformación y Metástasis

Eva González Jefe de Grupo
T +34 912246912 (Ext 3550)
egonzalez@cnio.es

Investigadores

María Jiménez

Becarios Pre-Doctorales

Marina Císcar

Current therapies for breast cancer and other epithelial tumors are in many cases not effective because of intrinsic or acquired resistance and tumors often relapse leading to metastatic disease. Research in the Transformation and Metastasis group aims to identify novel therapeutic targets for cancer prevention and treatment and to elucidate resistance mechanisms to drugs currently available. Tumors exploit and manipulate for their benefit the same mechanisms that work correctly in the healthy tissue. Thus, we first aim to understand normal development and identify the key events that lead to tumor initiation, progression and metastasis to avoid and combat them. We work with primary cell cultures (including 3D) cultures, genetically modified mouse models, patient derived xenografts and clinical samples.

Publicaciones

Gómez-Miragaya J, Morán S, Calleja-Cervantes ME, Collado-Solé A, Paré L, Gómez A, Serra V, Dobrolecki LE, Lewis MT, Diaz-Lagares A, Eroles P, Prat A, Esteller M, González-Suárez E. (2019). The altered transcriptome and DNA methylation profiles of docetaxel resistance in breast cancer PDX models.. Mol Cancer Res (in press).
Gómez-Miragaya J, Díaz-Navarro A, Tonda R, Beltran S, Palomero L, Palafox M, Dobrolecki LE, Huang C, Vasaikar S, Zhang B, Wulf GM, Collado-Sole A, Trinidad EM, Muñoz P, Paré L, Prat A, Bruna A, Caldas C, Arribas J, Soler-Monso MT, Petit A, Balmaña J, Cruz C, Serra V, Pujana MA, Lewis MT, Puente XS, González-Suárez E (2019). Chromosome 12p Amplification in Triple-Negative/BRCA1-Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity.. Cancer Res 79, 4258-4270.
von Moos R, Costa L, Gonzalez-Suarez E, Terpos E, Niepel D, Body JJ. (2019). Management of bone health in solid tumours: From bisphosphonates to a monoclonal antibody.. Cancer Treat Rev 76, 57-67.
Bernat-Peguera A, Simón-Extremera P, da Silva-Diz V, López de Munain M, Díaz-Gil L, Penin RM, González-Suárez E, Pérez Sidelnikova D, Bermejo O, Viñals JM, Viñals F, Muñoz P. (2019). PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma.. Oncogene 38, 5021-5037.
Piqué L, Martinez de Paz A, Piñeyro D, Martínez-Cardús A, Castro de Moura M, Llinàs-Arias P, Setien F, Gomez-Miragaya J, Gonzalez-Suarez E, Sigurdsson S, Jonasson JG, Villanueva A, Vidal A, Davalos V, Esteller M (2019). Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer.. Oncogene (in press).
Cánovas B, Igea A, Sartori AA, Gomis RR, Paull TT, Isoda M, Pérez-Montoyo H, Serra V, González-Suárez E, Stracker TH, Nebreda AR (2018). Targeting p38a Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells.. Cancer Cell 33, 1094-1110.
Koledova Z, Howard BA, Englund J, Bach K, Bentires-Alj M, Gonzalez-Suarez E (2018). European Network of Breast Development and Cancer turned 10 years: a growing family of mammary gland researchers.. Breast Cancer Res 20, 102.
Ruiz de Garibay G, Herranz C, Llorente A, Boni J, Serra-Musach J, Mateo F, Aguilar H, Gómez-Baldó L, Petit A, Vidal A, Climent F, Hernández-Losa J, Cordero Á, González-Suárez E, Sánchez-Mut JV, Esteller M, Llatjós R, Varela M, López JI, García N, Extremera AI, Gumà A, Ortega R, Plà MJ, Fernández A, Pernas S, Falo C, Morilla I, Campos M, Gil M, Román A, Molina-Molina M, Ussetti P, Laporta R, Valenzuela C, Ancochea J, Xaubet A, Casanova Á, Pujana MA. (2018). Correction: Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness.. PLoS One 13, e0207586.
Ruiz de Garibay G, Herranz C, Llorente A, Boni J, Serra-Musach J, Mateo F, Aguilar H, Gómez-Baldó L, Petit A, Vidal A, Climent F, Hernández-Losa J, Cordero Á, González-Suárez E, Sánchez-Mut JV, Esteller M, Llatjós R, Varela M, López JI, García N, Extremera AI, Gumà A, Ortega R, Plà MJ, Fernández A, Pernas S, Falo C, Morilla I, Campos M, Gil M, Román A, Molina-Molina M, Ussetti P, Laporta R, Valenzuela C, Ancochea J, Xaubet A, Casanova Á, Pujana MA (2018). Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness. PLoS One 13, e0207586.
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 (2017). Interrogating open issues in cancer medicine with patient-derived xenografts.. Nat Rev Cancer 17, 632.
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 (2017). Interrogating open issues in cancer precision medicine with patient-derived xenografts.. Nat Rev Cancer 17, 254-268.
Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, Maicas M, Du S, Iorio F, Herranz-Ors C, Islam A, Prado X, Llorente A, Petit A, Vidal A, Català I, Soler T, Venturas G, Rojo-Sebastian A, Serra H, Cuadras D, Blanco I, Lozano J, Canals F, Sieuwerts AM, de Weerd V, Look MP, Puertas S, García N, Perkins AS, Bonifaci N, Skowron M, Gómez-Baldó L, Hernández V, Martínez-Aranda A, Martínez-Iniesta M, Serrat X, Cerón J, Brunet J, Barretina MP, Gil M, Falo C, Fernández A, Morilla I, Pernas S, Plà MJ, Andreu X, Seguí MA, Ballester R, Castellà E, Nellist M, Morales S, Valls J, Velasco A, Matias-Guiu X, Figueras A, Sánchez-Mut JV, Sánchez-Céspedes M, Cordero A, Gómez-Miragaya J, Palomero L, Gómez A, Gajewski TF, Cohen EEW, Jesiotr M, Bodnar L, Quintela-Fandino M, López-Bigas N, Valdés-Mas R, Puente XS, Viñals F, Casanovas O, Graupera M, Hernández-Losa J, Ramón Y Cajal S, García-Alonso L, Saez-Rodriguez J, Esteller M, Sierra A, Martín-Martín N, Matheu A, Carracedo A, González-Suárez E, Nanjundan M, Cortés J, Lázaro C, Odero MD, Martens JWM, Moreno-Bueno G, Barcellos-Hoff MH, Villanueva A, Gomis RR, Pujana MA (2017). Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.. Oncogene 36, 2737-2749.
Gómez-Miragaya J, Palafox M, Paré L, Yoldi G, Ferrer I, Vila S, Galván P, Pellegrini P, Pérez-Montoyo H, Igea A, Muñoz P, Esteller M, Nebreda AR, Urruticoechea A, Morilla I, Pernas S, Climent F, Soler-Monso MT, Petit A, Serra V, Prat A, González-Suárez E (2017). Resistance to Taxanes in Triple-Negative Breast Cancer Associates with the Dynamics of a CD49f+ Tumor-Initiating Population.. Stem Cell Reports 8, 1392-1407.
Pérez-Salvia M, Simó-Riudalbas L, Llinàs-Arias P, Roa L, Setien F, Soler M, de Moura MC, Bradner JE, Gonzalez-Suarez E, Moutinho C, Esteller M. (2017). Bromodomain inhibition shows antitumoral activity in mice and human luminal breast cancer.. Oncotarget 8, 51621-51629.
Gomez-Miragaya J, González-Suárez E (2017). Tumor-initiating CD49f cells are a hallmark of chemoresistant triple negative breast cancer.. Mol Cell Oncol 4, e1338208.
Dobrolecki LE, Airhart SD, Alferez DG, Aparicio S, Behbod F, Bentires-Alj M, Brisken C, Bult CJ, Cai S, Clarke RB, Dowst H, Ellis MJ, Gonzalez-Suarez E, Iggo RD, Kabos P, Li S, Lindeman GJ, Marangoni E, McCoy A, Meric-Bernstam F, Piwnica-Worms H, Poupon MF, Reis-Filho J, Sartorius CA, Scabia V, Sflomos G, Tu Y, Vaillant F, Visvader JE, Welm A, Wicha MS, Lewis MT (2016). Patient-derived xenograft (PDX) models in basic and translational breast cancer research.. Cancer Metast Rev 35, 547-573.
Trinidad EM, González-Suárez E (2016). RANKL inhibitors for osteosarcoma treatment: hope and caution.. Ann Transl Med 4, 534.
Sigl V, Owusu-Boaitey K, Joshi PA, Kavirayani A, Wirnsberger G, Novatchkova M, Kozieradzki I, Schramek D, Edokobi N, Hersl J, Sampson A, Odai-Afotey A, Lazaro C, Gonzalez-Suarez E, Pujana MA, Cimba F, Heyn H, Vidal E, Cruickshank J, Berman H, Sarao R, Ticevic M, Uribesalgo I, Tortola L, Rao S, Tan Y, Pfeiler G, Lee EY, Bago-Horvath Z, Kenner L, Popper H, Singer C, Khokha R, Jones LP, Penninger JM. (2016). RANKL/RANK control Brca1 mutation- .. Cell Res 26, 761-774.
da Silva-Diz V, Simón-Extremera P, Bernat-Peguera A, de Sostoa J, Urpí M, Penín RM, Sidelnikova DP, Bermejo O, Viñals JM, Rodolosse A, González-Suárez E, Moruno AG, Pujana MÁ, Esteller M, Villanueva A, Viñals F, Muñoz P (2016). Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression. Cancer Res 76, 1245-1259.
Yoldi G, Pellegrini P, Trinidad EM, Cordero A, Gomez-Miragaya J, Serra-Musach J, Dougall WC, Muñoz P, Pujana MA, Planelles L, González-Suárez E (2016). RANK Signaling Blockade Reduces Breast Cancer Recurrence by Inducing Tumor Cell Differentiation. Cancer Res 76, 5857-5869.
Cordero A, Pellegrini P, Sanz-Moreno A, Trinidad EM, Serra-Musach J, Deshpande C, Dougall WC, Pujana MA, González-Suárez E (2016). Rankl Impairs Lactogenic Differentiation Through Inhibition of the Prolactin/Stat5 Pathway at Midgestation. Stem Cells 34, 1027-1039.
González-Suárez E, Sanz-Moreno A (2016). RANK as a therapeutic target in cancer. FEBS J 283, 2018-2033.
Martínez-Aranda A, Hernández V, Guney E, Muixí L, Foj R, Baixeras N, Cuadras D, Moreno V, Urruticoechea A, Gil M, Oliva B, Moreno F, González-Suarez E, Vidal N, Andreu X, Seguí MA, Ballester R, Castella E, Sierra A. (2015). FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies. Oncotarget 6, 44254-44273.
García-Castro A, Zonca M, Florindo-Pinheiro D, Carvalho-Pinto CE, Cordero A, Gutiérrez del Fernando B, García-Grande A, Mañes S, Hahne M, González-Suárez E, Planelles L (2015). APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer. Carcinogenesis 36, 574-584.
Blancafort A, Giró-Perafita A, Oliveras G, Palomeras S, Turrado C, Campuzano Ò, Carrión-Salip D, Massaguer A, Brugada R, Palafox M, Gómez-Miragaya J, González-Suárez E, Puig T (2015). Dual fatty acid synthase and HER2 signaling blockade shows marked antitumor activity against breast cancer models resistant to anti-HER2 drugs. PLoS One 10, e0131241.
Carmona FJ, Davalos V, Vidal E, Gomez A, Heyn H, Hashimoto Y, Vizoso M, Martinez-Cardus A, Sayols S, Ferreira HJ, Sánchez-Mut JV, Morán S, Margelí M, Castella E, Berdasco M, Stefansson OA, Eyfjord JE, Gonzalez-Suarez E, Dopazo J, Orozco M, Gut IG, Esteller M (2014). A comprehensive DNA methylation profile of epithelial-to-mesenchymal transition. Cancer Res 74, 5608-5619.
Ng K, Scott JB, Drake BF, Chan AT, Hollis BW, Chandler PD, Bennett GG, Giovannucci EL, Gonzalez-Suarez E, Meyerhardt JA, Emmons KM, Fuchs CS (2014). Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial.. Am J Clin Nutr 99, 587-598.
Dougall WC, Holen I, González Suárez E (2014). Targeting RANKL in metastasis.. BoneKey Rep 3, 519.
Allen JD, Pérez JE, Pischke CR, Tom LS, Juarez A, Ospino H, Gonzalez-Suarez E (2014). Dimensions of religiousness and cancer screening behaviors among church-going Latinas.. J Relig Health 53, 190-203.
Pellegrini P, Cordero A, Gallego MI, Dougall WC, Muñoz P, Pujana MA, Gonzalez-Suarez E. (2013). Constitutive activation of RANK disrupts mammary cell fate leading to tumorigenesis.. Stem Cells 31, 1954-1965.
Woo Baidal JA, Price SN, Gonzalez-Suarez E, Gillman MW, Mitchell K, Rifas-Shiman SL, Horan CM, Gortmaker SL, Taveras EM (2013). Parental perceptions of a motivational interviewing-based pediatric obesity prevention intervention.. Clin Pediatr 52, 540-548.
Palafox M, Ferrer I, Pellegrini P, Vila S, Hernandez-Ortega S, Urruticoechea A, Climent F, Soler MT, Muñoz P, Viñals F, Tometsko M, Branstetter D, Dougall WC, González-Suárez E (2012). RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res 72, 2879-2888.
Tarragona M, Pavlovic M, Arnal-Estapé A, Urosevic J, Morales M, Guiu M, Planet E, González-Suárez E, Gomis RR (2012). Identification of NOG as a specific breast cancer bone metastasis-supporting gene.. J Biol Chem 287, 21346-21355.
González-Suárez E (2011). RANKL inhibition: a promising novel strategy for breast cancer treatment. Clin Transl Oncol 13, 222-228.
Gonzalez-Suarez E, Jacob AP, Jones J, Miller R, Roudier-Meyer MP, Erwert R, Pinkas J, Branstetter D, Dougall WC (2010). RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 468, 103-107.
Arnett HA, Escobar SS, Gonzalez-Suarez E, Budelsky AL, Steffen LA, Boiani N, Zhang M, Siu G, Brewer AW, Viney JL (2007). BTNL2, a butyrophilin/B7-like molecule, is a negative costimulatory molecule modulated in intestinal inflammation.. J Immunol 178, 1523-1533.
Gonzalez-Suarez E, Branstetter D, Armstrong A, Dinh H, Blumberg H, Dougall WC (2007). RANK overexpression in transgenic mice with mouse mammary tumor virus promoter-controlled RANK increases proliferation and impairs alveolar differentiation in the mammary epithelia and disrupts lumen formation in cultured epithelial acini. Mol Cell Biol 27, 1442-1454.
Geserick C, Tejera A, González-Suárez E, Klatt P, Blasco MA (2006). Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling. Oncogene 25, 4310-4319.
Lobb R, Gonzalez Suarez E, Fay ME, Gutheil CM, Hunt MK, Fletcher RH, Emmons KM (2004). Implementation of a cancer prevention program for working class, multiethnic populations.. Prev Med 38, 766-776.
González-Suárez E, Goytisolo FA, Flores JM, Blasco MA (2003). Telomere dysfunction results in enhanced organismal sensitivity to the alkylating agent N-methyl-N-nitrosourea.. Cancer Res 63, 7047-7050.
Samper, E., Goytisolo, F. A., Menissier-de Murcia, J., González-Suárez, E., Cigudosa, J. C., de Murcia, G., Blasco, M. A. (2001). Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase-deficient mice and primary cells despite increased chromosomal instability.. J Cell Biol 154, 49-60.
González-Suárez, E., Samper, E., Ramirez, A., Flores, J. M., Martín-Caballero, J., Jorcano, J. L., Blasco, M. A. (2001). Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes.. EMBO J 20, 2619-2630.
Sachsinger J, González-Suárez E, Samper E, Heicappell R, Müller M, Blasco MA (2001). Telomerase inhibition in RenCa, a murine tumor cell line with short telomeres, by overexpression of a dominant negative mTERT mutant, reveals fundamental differences in telomerase regulation between human and murine cells.. Cancer Res 61, 5580-5586.
González-Suárez E, Samper E, Flores JM, Blasco MA (2000). Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat Genet 26, 114-117.