Cell Division and Cancer Group

Marcos Malumbres Group Leader
T +34 917328000 (Ext 3450)
mmm@cnio.es

Staff Scientists

Mónica Álvarez

Post-Doctoral Fellows

Carolina Maestre
María Salazar
Carolina Villarroya

Graduate Students

José González
Diego Martínez

Technicians

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.

Publications

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). CNIO Publication.
Malumbres M (2019). CDK4/6 inhibitors: what is the best cocktail?. Clin Cancer Res 25, 6-8. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. 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). CNIO Publication.
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. CNIO Publication. 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. CNIO Publication.
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. CNIO Publication. 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. CNIO Publication. 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. CNIO Publication. 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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication.
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). CNIO Publication.
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. CNIO Publication.
Burgess A, Vuong J, Rogers S, Malumbres M, O'Donoghue SI (2017). SnapShot: phosphoregulation of mitosis. Cell 169, 1358-1358e1. CNIO Publication.
Salazar-Roa M, Malumbres M. (2017). Fueling the Cell Division Cycle.. Trends Cell Biol 27, 69-81. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
Malumbres M (2016). CDK4/6 Inhibitors resTORe Therapeutic Sensitivity in HER2(+) Breast Cancer.. Cancer Cell 29, 243-244. CNIO Publication.
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. CNIO Publication.
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 Commun 7, 11389. CNIO Publication. Open Access
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 44, 5557-5570. CNIO Publication. Open Access
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. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
Álvarez-Fernández M, Malumbres M (2015). An Atypical Oncogene Within the Atypical E2Fs.. J Natl Cancer I 107, djv180. CNIO Publication.
Esteban-Martínez L, Doménech E, Boya P, Salazar-Roa M, Malumbres M (2015). Mitophagy in mitosis: more than a myth.. Autophagy 11, 2379-2380. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
Malumbres M (2015). Keeping Order in Anaphase.. Dev Cell 35, 403-404. CNIO Publication.
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. CNIO Publication.
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). CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
de Cárcer G, Malumbres M (2014). A centrosomal route for cancer genome instability.. Nat Cell Biol 16, 504-506. CNIO Publication.
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. CNIO Publication.
Trakala M, Malumbres M (2014). Cyclin C surprises in tumour suppression.. Nat Cell Biol 16, 1031-1033. CNIO Publication.
Malumbres M (2014). Cyclin-dependent kinases.. Genome Biol 15, 122. CNIO Publication.
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. CNIO Publication.
Valcárcel J, Malumbres M (2014). Splicing together sister chromatids.. EMBO J 33, 2601-2603. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
Malumbres M, Pérez de Castro I (2014). Aurora kinase A inhibitors: promising agents in antitumoral therapy.. Expert Opin Ther Tar 9, 1-17. CNIO Publication.
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. CNIO Publication.
Trakala M, Malumbres M (2014). The functional relevance of polyploidization in the skin. Exp Dermatol 23, 92-93. CNIO Publication.
Wang P, Malumbres M, Archambault V (2014). The Greatwall-PP2A axis in cell cycle control.. Methods Mol Biol 1170, 99-111. CNIO Publication.