Grupo de División Celular y Cáncer

Marcos Malumbres Jefe de Grupo
T +34 917328000 (Ext 3450)
mmm@cnio.es

Investigadores

Mónica Álvarez

Becarios Post-doctorales

Carolina Maestre
María Salazar
Carolina Villarroya

Becarios Pre-Doctorales

José González
Diego Martínez

Técnicos de Laboratorio

Aicha El Bakkali
Elisabet Zapatero

The Cell Division and Cancer Group is interested in deciphering the mechanisms by which cell division and cell proliferation are regulated in mammalian cells. During the last years, we have used different mouse models to understand the relevance of cell cycle regulators, including cell cycle kinases and phosphatases, as well as proteins involved in ubiquitin-dependent degradation, in the control of cell division and tissue physiology.

Our interests are:

To understand the basic control mechanisms that regulate the cell division cycle.
To characterise the physiological and therapeutic consequences of cell cycle deregulation.
Understanding self-renewal and pluripotency in stem cell biology and tumour development.
To find and validate new targets for cancer therapy. As a final goal, we aim to generate information that may be useful to improve therapeutic strategies against cancer cell proliferation.

Publicaciones

Tomás-Loba A, Manieri E, González-Terán B, Mora A, Leiva-Vega L, Santamans AM, Romero-Becerra R, Rodríguez E, Pintor-Chocano A, Feixas F, López JA, Caballero B, Trakala M, Blanco Ó, Torres JL, Hernández-Cosido L, Montalvo-Romeral V, Matesanz N, Roche-Molina M, Bernal JA, Mischo H, León M, Caballero A, Miranda-Saavedra D, Ruiz-Cabello J, Nevzorova YA, Cubero FJ, Bravo J, Vázquez J, Malumbres M, Marcos M, Osuna S, Sabio G (2019). p38? is essential for cell cycle progression and liver tumorigenesis. Nature (in press).
Malumbres M (2019). CDK4/6 inhibitors: what is the best cocktail?. Clin Cancer Res 25, 6-8.
Garcia-Carpizo V, Ruiz-Llorente S, Sarmentero J, González-Corpas A, Barrero MJ (2019). CREBBP/EP300 Bromodomain Inhibition Affects the Proliferation of AR-Positive Breast Cancer Cell Lines. Mol Cancer Res 13, 720-730.
Bustos-Morán E, Blas-Rus N, Alcaraz-Serna A, Iborra S, González-Martínez J, Malumbres M, Sánchez-Madrid F (2019). Aurora A controls CD8+ T cell cytotoxic activity and antiviral response. Sci Rep 3, 2211. Open Access
Vázquez-Domínguez I, González-Sánchez L, López-Nieva P, Fernández-Navarro P, Villa-Morales M, Cobos-Fernández MÁ, Sastre I, F Fraga M, F Fernández A, Malumbres M, Salazar-Roa M, Graña-Castro O, Santos J, Llamas P, López-Lorenzo JL, Fernández-Piqueras J (2019). Downregulation of specific FBXW7 isoforms with differential effects in T-cell lymphoblastic lymphoma. Oncogene (in press).
López-Nieva P, Fernández-Navarro P, Graña-Castro O, Andrés-León E, Santos J, Villa-Morales M, Cobos-Fernández MÁ, González-Sánchez L, Malumbres M, Salazar-Roa M, Fernández-Piqueras J (2019). Detection of novel fusion-transcripts by RNA-Seq in T-cell lymphoblastic lymphoma. Sci Rep 9, 5179. Open Access
Bellutti F, Tigan AS, Nebenfuehr S, Dolezal M, Zojer M, Grausenburger R, Hartenberger S, Kollmann S, Doma E, Prchal-Murphy M, Uras IZ, Höllein A, Neuberg DS, Ebert BL, Ringler A, Mueller AC, Loizou JI, Hinds PW, Vogl C, Heller G, Kubicek S, Zuber J, Malumbres M, Farlik M, Villunger A, Kollmann K, Sexl V (2018). CDK6 Antagonizes p53-Induced Responses during Tumorigenesis. Cancer Discovery 8, 884-897.
Hurtado B, Trakala M, Ximénez-Embún P, El-Bakkali A, Partida D, Sanz-Castillo B, Álvarez-Fernández M, Maroto M, Sánchez-Martínez R, Martínez L, Muñoz J, García de Frutos P, Malumbres M (2018). Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeleton dynamics in platelets. J Clin Invest 128, 5351-5367. Open Access
de Cárcer G, Venkateswaran SV, Salgueiro L, El Bakkali A, Somogyi K, Rowald K, Montañés P, Sanclemente M, Escobar B, de Martino A, McGranahan N, Malumbres M, Sotillo R (2018). Plk1 overexpression induces chromosomal instability and suppresses tumor development. Nat Commun 9, 3012. Open Access
Mitxelena J, Apraiz A, Vallejo-Rodríguez J, García-Santisteban I, Fullaondo A, Alvarez-Fernández M, Malumbres M, Zubiaga AM (2018). An E2F7-dependent transcriptional program modulates DNA damage repair and genomic stability. Nucleic Acids Res 46, 4546-4559. Open Access
Nguyen AL, Drutovic D, Vazquez BN, El Yakoubi W, Gentilello AS, Malumbres M, Solc P, Schindler K (2018). Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis. Curr Biol 28, 3458-3468.
Álvarez-Fernández M, Sanz-Flores M, Sanz-Castillo B, Salazar-Roa M, Partida D, Zapatero-Solana E, Ali HR, Manchado E, Lowe S, VanArsdale T, Shields D, Caldas C, Quintela-Fandino M, Malumbres M (2018). Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer. Cell Death Differ 25, 828-840.
Ovejero S, Ayala P, Malumbres M, Pimentel-Muiños FX, Bueno A, Sacristán MP (2018). Biochemical analyses reveal amino acid residues critical for cell cycle-dependent phosphorylation of human Cdc14A phosphatase by cyclin-dependent kinase 1. Sci Rep 8, 11871.
López-Nieva P, Fernández-Navarro P, Vaquero-Lorenzo C, Villa-Morales M, Graña-Castro O, Cobos-Fernández MÁ, López-Lorenzo JL, Llamas P, González-Sanchez L, Sastre I, Pollan M, Malumbres M, Santos J, Fernández-Piqueras J (2018). RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas. Bmc Cancer 18, 430.
Rata S, Suarez Peredo Rodriguez MF, Joseph S, Peter N, Echegaray Iturra F, Yang F, Madzvamuse A, Ruppert JG, Samejima K, Platani M, Alvarez-Fernandez M, Malumbres M, Earnshaw WC, Novak B, Hochegger H (2018). Two Interlinked Bistable Switches Govern Mitotic Control in Mammalian Cells. Curr Biol 28, 3824-3832.
Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer. (2017). Álvarez-Fernández M, Sanz-Flores M, Sanz-Castillo B, Salazar-Roa M, Partida D, Zapatero-Solana E, Ali HR, Manchado E, Lowe S, VanArsdale T, Shields D, Caldas C, Quintela-Fandino M, Malumbres M.. Cell Death Differ (in press).
de Cárcer G, Wachowicz P, Martínez-Martínez S, Oller J, Méndez-Barbero N, Escobar B, González-Loyola A, Takaki T, El Bakkali A, Cámara JA, Jiménez-Borreguero LJ, Bustelo XR, Cañamero M, Mulero F, de Los Ángeles Sevilla M, Montero MJ, Redondo JM, Malumbres M. (2017). Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis.. Nat Med 23, 964-974.
Burgess A, Vuong J, Rogers S, Malumbres M, O'Donoghue SI (2017). SnapShot: phosphoregulation of mitosis. Cell 169, 1358-1358e1.
Salazar-Roa M, Malumbres M. (2017). Fueling the Cell Division Cycle.. Trends Cell Biol 27, 69-81.
Ha K, Ma C, Lin H, Tang L, Lian Z, Zhao F, Li J-M, Zhen B, Pei H, Han S, Malumbres M, Jin J, Chen H, Zhao Y, Zhu Q, Zhang P (2017). The anaphase promoting complex impacts repair choice by protecting ubiquitin signaling at DNA damage sites. Nat Commun 8, 15751.
Esteban-Martínez L, Sierra-Filardi E, McGreal RS, Salazar-Roa M, Mariño G, Seco E, Durand S, Enot D, Graña O, Malumbres M, Cvekl A, Cuervo AM, Kroemer G, Boya P (2017). Programmed mitophagy is essential for the glycolytic switch during cell differentiation.. EMBO J 36, 1688-1706.
Rattani A, Ballesteros Mejia R, Roberts K, Roig MB, Godwin J, Hopkins M, Eguren M, Sanchez-Pulido L, Okaz E, Ogushi S, Wolna M, Metson J, Pendás AM, Malumbres M, Novák B, Herbert M, Nasmyth K (2017). APC/CCdh1 enables removal of shugoshin-2 from the arms of bivalent chromosomes by moderating cyclin-dependent kinase activity. Curr Biol 27, 1462-1476.
Hydbring P, Malumbres M, Sicinski P (2016). Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases.. Nat Rev Mol Cell Bio 17, 280-292.
Malumbres M (2016). CDK4/6 Inhibitors resTORe Therapeutic Sensitivity in HER2(+) Breast Cancer.. Cancer Cell 29, 243-244.
Shao R, Liu J, Yan G, Zhang J, Han Y, Guo J, Xu Z, Yuan Z, Liu J, Malumbres M, Wan L, Wei W, Zou W (2016). Cdh1 regulates craniofacial development via APC-dependent ubiquitination and activation of Goosecoid.. Cell Res 26, 699-712.
Blas-Rus N, Bustos-Morán E, Pérez de Castro I, de Cárcer G, Borroto A, Camafeita E, Jorge I, Vázquez J, Alarcón B, Malumbres M, Martín-Cófreces NB, Sánchez-Madrid F (2016). Aurora A drives early signalling and vesicle dynamics during T-cell activation.. Nat Communications 7, 11389.
Mitxelena J, Apraiz A, Vallejo-Rodríguez J, Malumbres M, Zubiaga AM (2016). E2F7 regulates transcription and maturation of multiple microRNAs to restrain cell proliferation.. Nucleic Acids Res (in press).
Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Llères D, Gerbe F, Prieto S, Krasinska L, David A, Eguren M, Birling MC, Urbach S, Hem S, Déjardin J, Malumbres M, Jay P, Dulic V, Lafontaine DLj, Feil R, Fisher D (2016). The cell proliferation antigen Ki-67 organises heterochromatin.. Elife 5, e13722.
Quereda V, Porlan E, Cañamero M, Dubus P, Malumbres M (2016). An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress.. Cell Death Differ 23, 430-441.
Correia NC, Melão A, Póvoa V, Sarmento L, Gómez de Cedrón M, Malumbres M, Enguita FJ, Barata JT (2016). microRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia.. Oncotarget 7, 8268-8281.
Liu J, Wan L, Liu J, Yuan Z, Zhang J, Guo J, Malumbres M, Liu J, Zou W, Wei W (2016). Cdh1 inhibits WWP2-mediated ubiquitination of PTEN to suppress tumorigenesis in an APC-independent manner.. Cell Discov 2, 15044.
Doménech E, Maestre C, Esteban-Martínez L, Partida D, Pascual R, Fernández-Miranda G, Seco E, Campos-Olivas R, Pérez M, Megias D, Allen K, López M, Saha AK, Velasco G, Rial E, Méndez R, Boya P, Salazar-Roa M, Malumbres M (2015). AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest.. Nat Cell Biol 17, 1304-1316.
Huang J, Ikeuchi Y, Malumbres M, Bonni A (2015). A Cdh1-APC/FMRP Ubiquitin Signaling Link Drives mGluR-Dependent Synaptic Plasticity in the Mammalian Brain.. Neuron 86, 726-739.
Álvarez-Fernández M, Malumbres M (2015). An Atypical Oncogene Within the Atypical E2Fs.. J Natl Cancer I 107, djv180.
Esteban-Martínez L, Doménech E, Boya P, Salazar-Roa M, Malumbres M (2015). Mitophagy in mitosis: more than a myth.. Autophagy 11, 2379-2380.
Serra H, Chivite I, Angulo-Urarte A, Soler A, Sutherland JD, Arruabarrena-Aristorena A, Ragab A, Lim R, Malumbres M, Fruttiger M, Potente M, Serrano M, Fabra À, Viñals F, Casanovas O, Pandolfi PP, Bigas A, Carracedo A, Gerhardt H, Graupera M (2015). PTEN mediates Notch-dependent stalk cell arrest in angiogenesis.. Nat Communications 6, 7935.
Scheicher R, Hoelbl-Kovacic A, Bellutti F, Tigan AS, Prchal-Murphy M, Heller G, Schneckenleithner C, Salazar-Roa M, Zöchbauer-Müller S, Zuber J, Malumbres M, Kollmann K, Sexl V (2015). CDK6 as a key regulator of hematopoietic and leukemic stem cell activation.. Blood 125, 90-101.
Trakala M, Partida D, Salazar-Roa M, Maroto M, Wachowicz P, de Cárcer G, Malumbres M (2015). Activation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice.. Blood 126, 1707-1714.
Malumbres M (2015). Keeping Order in Anaphase.. Dev Cell 35, 403-404.
Penas C, Govek EE, Fang Y, Ramachandran V, Daniel M, Wang W, Maloof ME, Rahaim RJ, Bibian M, Kawauchi D, Finkelstein D, Han JL, Long J, Li B, Robbins DJ, Malumbres M, Roussel MF, Roush WR, Hatten ME, Ayad NG (2015). Casein kinase 1d is an APC/C(Cdh1) substrate that regulates cerebellar granule cell neurogenesis.. Cell Reports 11, 249-260.
Quereda V, Porlan E, Cañamero M, Dubus P, Malumbres M (2015). An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress.. Cell Death Differ (in press).
Sánchez-Martínez R, Cruz-Gil S, Gómez de Cedrón M, Álvarez-Fernández M, Vargas T, Molina S, García B, Herranz J, Moreno-Rubio J, Reglero G, Pérez-Moreno M, Feliú J, Malumbres M, Ramírez de Molina A (2015). A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy.. Oncotarget 6, 38719-39736.
González-Loyola A, Fernández-Miranda G, Trakala M, Partida D, Samejima K, Ogawa H, Cañamero M, de Martino A, Martínez-Ramírez Á, de Cárcer G, Pérez de Castro I, Earnshaw WC, Malumbres M (2015). Aurora B overexpression causes aneuploidy and p21Cip1 repression during tumor development.. Mol Cell Biol 35, 3566-3578.
Búa S, Sotiropoulou P, Sgarlata C, Borlado, LR, Eguren M, Domínguez O, Ortega S, Malumbres M, Blanpain C, Méndez J (2015). Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.. Cell Cycle 14, 3897-3907.
Trakala M, Rodríguez-Acebes S, Maroto M, Symonds CE, Santamaría D, Ortega S, Barbacid M, Méndez J, Malumbres M. (2015). Functional reprogramming of polyploidization in megakaryocytes.. Dev Cell 32, 155-167.
Piazzolla D, Palla AR, Pantoja C, Cañamero M, de Castro IP, Ortega S, Gómez-López G, Dominguez O, Megías D, Roncador G, Luque-Garcia JL, Fernandez-Tresguerres B, Fernandez AF, Fraga MF, Rodriguez-Justo M, Manzanares M, Sánchez-Carbayo M, García-Pedrero JM, Rodrigo JP, Malumbres M, Serrano M (2014). Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia.. Nat Communications 5, 4226.
Eguren M, Álvarez-Fernández M, García F, López-Contreras AJ, Fujimitsu K, Yaguchi H, Luque-García JL, Fernández-Capetillo O, Muñoz J, Yamano H, Malumbres M (2014). A synthetic lethal interaction between APC/C and topoisomerase poisons uncovered by proteomic screens.. Cell Reports 6, 670-683.
de Cárcer G, Malumbres M (2014). A centrosomal route for cancer genome instability.. Nat Cell Biol 16, 504-506.
Porlan E, Martí-Prado B, Morante-Redolat JM, Consiglio A, Delgado AC, Kypta R, López-Otín C, Kirstein M, Fariñas I (2014). MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin.. Nat Cell Biol 16, 629-638.
Trakala M, Malumbres M (2014). Cyclin C surprises in tumour suppression.. Nat Cell Biol 16, 1031-1033.
Malumbres M (2014). Cyclin-dependent kinases.. Genome Biol 15, 122.
Rodríguez-Díez E, Quereda V, Bellutti F, Prchal-Murphy M, Partida D, Eguren M, Gómez de Cedrón M, Dubus P, Cañamero M, Martínez D, Sexl V, Malumbres M (2014). Cdk4 and Cdk6 cooperate in counteracting the INK4 family of inhibitors during murine leukemogenesis.. Blood 124, 2380-2390.
Valcárcel J, Malumbres M (2014). Splicing together sister chromatids.. EMBO J 33, 2601-2603.
Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, Malumbres M, Letai A, Kirschner MW, Sun Y, Wei W (2014). APC(Cdc20) Suppresses Apoptosis through Targeting Bim for Ubiquitination and Destruction.. Dev Cell 29, 377-391.
Rattani A, Vinod PK, Godwin J, Tachibana-Konwalski K, Wolna M, Malumbres M, Novák B, Nasmyth K (2014). Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase transition irreversible.. Curr Biol 24, 630-637.
Malumbres M, Pérez de Castro I (2014). Aurora kinase A inhibitors: promising agents in antitumoral therapy.. Expert Opin Ther Tar 9, 1-17.
Alvarez-Fernández M, Malumbres M (2014). Preparing a cell for nuclear envelope breakdown: Spatio-temporal control of phosphorylation during mitotic entry.. Bioessays 36, 757-765.
Trakala M, Malumbres M (2014). The functional relevance of polyploidization in the skin. Exp Dermatol 23, 92-93.
Wang P, Malumbres M, Archambault V (2014). The Greatwall-PP2A axis in cell cycle control.. Methods Mol Biol 1170, 99-111.
Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, Schäfer M, Fajmann S, Schlederer M, Schiefer AI, Reichart U, Mayerhofer M, Hoeller C, Zöchbauer-Müller S, Kerjaschki D, Bock C, Kenner L, Hoefler G, Freissmuth M, Green AR, Moriggl R, Busslinger M, Malumbres M, Sexl V (2013). A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.. Cancer Cell 24, 167-181.
Frangini A, Sjöberg M, Roman-Trufero M, Dharmalingam G, Haberle V, Bartke T, Lenhard B, Malumbres M, Vidal M, Dillon N (2013). The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.. Mol Cell 51, 647-661.
Kim JA, Aberg C, de Cárcer G, Malumbres M, Salvati A, Dawson KA (2013). Low Dose of Amino-Modified Nanoparticles Induces Cell Cycle Arrest.. ACS Nano 7, 7483-7494.
Eguren M, Porlan E, Manchado E, García-Higuera I, Cañamero M, Fariñas I, Malumbres M (2013). The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors.. Nat Communications 4, 2880.
Malumbres M (2013). miRNAs and cancer: an epigenetics view.. Mol Aspects Med 34, 863-874.
Alvarez-Fernández M, Sánchez-Martínez R, Sanz-Castillo B, Gan PP, Sanz-Flores M, Trakala M, Ruiz-Torres M, Lorca T, Castro A, Malumbres M (2013). Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.. Proc Natl Acad Sci USA 110, 17374-17379.
Pérez de Castro I, Aguirre-Portolés C, Fernández-Miranda G, Cañamero M, Cowley DO, Van Dyke T, Malumbres M (2013). Requirements for aurora-a in tissue regeneration and tumor development in adult mammals.. Cancer Res 73, 6804-6815.
Parrillas V, Martínez-Muñoz L, Holgado BL, Kumar A, Cascio G, Lucas P, Rodríguez-Frade JM, Malumbres M, Carrera AC, van Wely KH, Mellado M (2013). Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells.. Cell Mol Life Sci 70, 545-558.
Doménech E, Malumbres M (2013). Mitosis-targeting therapies: a troubleshooting guide.. Curr Opin Pharmacol 13, 519-528.
González-Gugel E, Villa-Morales M, Santos J, Bueno MJ, Malumbres M, Rodríguez-Pinilla SM, Piris MÁ, Fernández-Piqueras J (2013). Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.. Carcinogenesis 34, 902-908.
Trakala M, Fernández-Miranda G, Pérez de Castro I, Heeschen C, Malumbres M (2013). Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21 (Cip1).. Cell Cycle 12, 1030-1041.
Pick JE, Malumbres M, Klann E (2013). The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice.. Learn Memory 20, 11-20.
Tuck C, Zhang T, Potapova T, Malumbres M, Novák B. (2013). Robust mitotic entry is ensured by a latching switch.. Biol Open 2, 924-931.
Alvarez-Fernández M, Medema RH (2013). Novel functions of FoxM1: from molecular mechanisms to cancer therapy.. Front Oncol 5, 30.
Michel CI, Malumbres M (2013). MicroRNA-203: tumor suppression and beyond.. MicroRNA 2, 118-126.