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

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 few years, we have used different mouse models to understand the relevance of cell cycle regulators, including cell cycle kinases and phosphatases, as well as of proteins involved in ubiquitin-dependent degradation, in the control of cell division and tissue physiology. Our interests are: i) to understand the basic control mechanisms that regulate the cell division cycle; ii) to characterise the physiological and therapeutic consequences of cell cycle deregulation; iii) understanding the function of microRNAs in stem cell biology and tumour development, and iv) to understand how progenitor cells and cancer stem cells control their self-renewal and proliferative properties. As a final goal, we aim to generate information that may be useful for improving therapeutic strategies against cancer cell proliferation.

Publications

• CDK4/6 inhibitors: what is the best cocktail?(2019)
  Malumbres M.
  Clin Cancer Res 25, 6-8.
• CDK6 Antagonizes p53-Induced Responses during Tumorigenesis.(2018)
  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.
  Cancer Discovery 8, 884-897.
• Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeleton dynamics in platelets(2018)
  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
  J Clin Invest 128, 5351-5367.
• Plk1 overexpression induces chromosomal instability and suppresses tumor development.(2018)
  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.
  Nat Commun 9, 3012-.
• An E2F7-dependent transcriptional program modulates DNA damage repair and genomic stability.(2018)
  Mitxelena J, Apraiz A, Vallejo-Rodríguez J, García-Santisteban I, Fullaondo A, Alvarez-Fernández M, Malumbres M, Zubiaga AM.
  Nucleic Acids Res 46, 4546-4559.
• Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis.(2018)
  Nguyen AL, Drutovic D, Vazquez BN, El Yakoubi W, Gentilello AS, Malumbres M, Solc P, Schindler K.
  Curr Biol 28, 3458-3468.
• Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer.(2018)
  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 25, 828-840.
• Biochemical analyses reveal amino acid residues critical for cell cycle-dependent phosphorylation of human Cdc14A phosphatase by cyclin-dependent kinase 1.(2018)
  Ovejero S, Ayala P, Malumbres M, Pimentel-Muiños FX, Bueno A, Sacristán MP.
  Sci Rep 8, 11871-.
• RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas.(2018)
  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.
  Bmc Cancer 18, 430-.
• Two Interlinked Bistable Switches Govern Mitotic Control in Mammalian Cells.(2018)
  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
  Curr Biol 28, 3824-3832.
• 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.(2017)
  Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer.
  Cell Death Differ (in press).
• Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis.(2017)
  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.
  Nat Med 23, 964-974.
• SnapShot: phosphoregulation of mitosis(2017)
  Burgess A, Vuong J, Rogers S, Malumbres M, O'Donoghue SI
  Cell 169, 1358-1358e1.
• Fueling the Cell Division Cycle.(2017)
  Salazar-Roa M, Malumbres M.
  Trends Cell Biol 27, 69-81.
• The anaphase promoting complex impacts repair choice by protecting ubiquitin signaling at DNA damage sites(2017)
  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
  Nat Commun 8, 15751-.
• Programmed mitophagy is essential for the glycolytic switch during cell differentiation.(2017)
  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
  EMBO J 36, 1688-1706.
• APC/CCdh1 enables removal of shugoshin-2 from the arms of bivalent chromosomes by moderating cyclin-dependent kinase activity(2017)
  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
  Curr Biol 27, 1462-1476.
• Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases.(2016)
  Hydbring P, Malumbres M, Sicinski P
  Nat Rev Mol Cell Bio 17, 280-292.
• CDK4/6 Inhibitors resTORe Therapeutic Sensitivity in HER2(+) Breast Cancer.(2016)
  Malumbres M
  Cancer Cell 29, 243-244.
• Cdh1 regulates craniofacial development via APC-dependent ubiquitination and activation of Goosecoid.(2016)
  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
  Cell Res 26, 699-712.
• Aurora A drives early signalling and vesicle dynamics during T-cell activation.(2016)
  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
  Nat Communications 7, 11389-.
• E2F7 regulates transcription and maturation of multiple microRNAs to restrain cell proliferation.(2016)
  Mitxelena J, Apraiz A, Vallejo-Rodríguez J, Malumbres M, Zubiaga AM
  Nucleic Acids Res (in press).
• The cell proliferation antigen Ki-67 organises heterochromatin.(2016)
  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
  Elife 5, e13722-.
• An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress.(2016)
  Quereda V, Porlan E, Cañamero M, Dubus P, Malumbres M
  Cell Death Differ 23, 430-441.
• microRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia.(2016)
  Correia NC, Melão A, Póvoa V, Sarmento L, Gómez de Cedrón M, Malumbres M, Enguita FJ, Barata JT
  Oncotarget 7, 8268-8281.
• Cdh1 inhibits WWP2-mediated ubiquitination of PTEN to suppress tumorigenesis in an APC-independent manner.(2016)
  Liu J, Wan L, Liu J, Yuan Z, Zhang J, Guo J, Malumbres M, Liu J, Zou W, Wei W
  Cell Discov 2, 15044-.
• Functional reprogramming of polyploidization in megakaryocytes.(2015)
  Trakala M, Rodríguez-Acebes S, Maroto M, Symonds CE, Santamaría D, Ortega S, Barbacid M, Méndez J, Malumbres M.
  Dev Cell 32, 155-167.
• AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest.(2015)
  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
  Nat Cell Biol 17, 1304-1316.
• A Cdh1-APC/FMRP Ubiquitin Signaling Link Drives mGluR-Dependent Synaptic Plasticity in the Mammalian Brain.(2015)
  Huang J, Ikeuchi Y, Malumbres M, Bonni A
  Neuron 86, 726-739.
• An Atypical Oncogene Within the Atypical E2Fs.(2015)
  Álvarez-Fernández M, Malumbres M
  J Natl Cancer I 107, djv180-.
• Mitophagy in mitosis: more than a myth.(2015)
  Esteban-Martínez L, Doménech E, Boya P, Salazar-Roa M, Malumbres M
  Autophagy 11, 2379-2380.
• PTEN mediates Notch-dependent stalk cell arrest in angiogenesis.(2015)
  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
  Nat Communications 6, 7935-.
• CDK6 as a key regulator of hematopoietic and leukemic stem cell activation.(2015)
  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
  Blood 125, 90-101.
• Activation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice.(2015)
  Trakala M, Partida D, Salazar-Roa M, Maroto M, Wachowicz P, de Cárcer G, Malumbres M
  Blood 126, 1707-1714.
• Keeping Order in Anaphase.(2015)
  Malumbres M
  Dev Cell 35, 403-404.
• Casein kinase 1d is an APC/C(Cdh1) substrate that regulates cerebellar granule cell neurogenesis.(2015)
  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
  Cell Reports 11, 249-260.
• An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress.(2015)
  Quereda V, Porlan E, Cañamero M, Dubus P, Malumbres M
  Cell Death Differ (in press).
• A link between lipid metabolism and epithelial-mesenchymal transition provides a target for colon cancer therapy.(2015)
  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
  Oncotarget 6, 38719-39736.
• Aurora B overexpression causes aneuploidy and p21Cip1 repression during tumor development.(2015)
  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
  Mol Cell Biol 35, 3566-3578.
• Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.(2015)
  Búa S, Sotiropoulou P, Sgarlata C, Borlado, LR, Eguren M, Domínguez O, Ortega S, Malumbres M, Blanpain C, Méndez J
  Cell Cycle 14, 3897-3907.
• A synthetic lethal interaction between APC/C and topoisomerase poisons uncovered by proteomic screens.(2014)
  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
  Cell Reports 6, 670-683.
• Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia.(2014)
  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
  Nat Communications 5, 4226-.
• A centrosomal route for cancer genome instability.(2014)
  de Cárcer G, Malumbres M
  Nat Cell Biol 16, 504-506.
• MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin.(2014)
  Porlan E, Martí-Prado B, Morante-Redolat JM, Consiglio A, Delgado AC, Kypta R, López-Otín C, Kirstein M, Fariñas I
  Nat Cell Biol 16, 629-638.
• Cyclin C surprises in tumour suppression.(2014)
  Trakala M, Malumbres M
  Nat Cell Biol 16, 1031-1033.
• Cyclin-dependent kinases.(2014)
  Malumbres M
  Genome Biol 15, 122-.
• Cdk4 and Cdk6 cooperate in counteracting the INK4 family of inhibitors during murine leukemogenesis.(2014)
  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
  Blood 124, 2380-2390.
• Splicing together sister chromatids.(2014)
  Valcárcel J, Malumbres M
  EMBO J 33, 2601-2603.
• APC(Cdc20) Suppresses Apoptosis through Targeting Bim for Ubiquitination and Destruction.(2014)
  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
  Dev Cell 29, 377-391.
• Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase transition irreversible.(2014)
  Rattani A, Vinod PK, Godwin J, Tachibana-Konwalski K, Wolna M, Malumbres M, Novák B, Nasmyth K
  Curr Biol 24, 630-637.
• Aurora kinase A inhibitors: promising agents in antitumoral therapy.(2014)
  Malumbres M, Pérez de Castro I
  Expert Opin Ther Tar 9, 1-17.
• Preparing a cell for nuclear envelope breakdown: Spatio-temporal control of phosphorylation during mitotic entry.(2014)
  Alvarez-Fernández M, Malumbres M
  Bioessays 36, 757-765.
• The functional relevance of polyploidization in the skin(2014)
  Trakala M, Malumbres M
  Exp Dermatol 23, 92-93.
• The Greatwall-PP2A axis in cell cycle control.(2014)
  Wang P, Malumbres M, Archambault V
  Methods Mol Biol 1170, 99-111.
• A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.(2013)
  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
  Cancer Cell 24, 167-181.
• The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.(2013)
  Frangini A, Sjöberg M, Roman-Trufero M, Dharmalingam G, Haberle V, Bartke T, Lenhard B, Malumbres M, Vidal M, Dillon N
  Mol Cell 51, 647-661.
• Low Dose of Amino-Modified Nanoparticles Induces Cell Cycle Arrest.(2013)
  Kim JA, Aberg C, de Cárcer G, Malumbres M, Salvati A, Dawson KA
  ACS Nano 7, 7483-7494.
• The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors.(2013)
  Eguren M, Porlan E, Manchado E, García-Higuera I, Cañamero M, Fariñas I, Malumbres M
  Nat Communications 4, 2880-.
• miRNAs and cancer: an epigenetics view.(2013)
  Malumbres M
  Mol Aspects Med 34, 863-874.
• Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.(2013)
  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
  Proc Natl Acad Sci USA 110, 17374-17379.
• Requirements for aurora-a in tissue regeneration and tumor development in adult mammals.(2013)
  Pérez de Castro I, Aguirre-Portolés C, Fernández-Miranda G, Cañamero M, Cowley DO, Van Dyke T, Malumbres M
  Cancer Res 73, 6804-6815.
• Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells.(2013)
  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
  Cell Mol Life Sci 70, 545-558.
• Mitosis-targeting therapies: a troubleshooting guide.(2013)
  Doménech E, Malumbres M
  Curr Opin Pharmacol 13, 519-528.
• Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development.(2013)
  González-Gugel E, Villa-Morales M, Santos J, Bueno MJ, Malumbres M, Rodríguez-Pinilla SM, Piris MÁ, Fernández-Piqueras J
  Carcinogenesis 34, 902-908.
• Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21 (Cip1).(2013)
  Trakala M, Fernández-Miranda G, Pérez de Castro I, Heeschen C, Malumbres M
  Cell Cycle 12, 1030-1041.
• The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice.(2013)
  Pick JE, Malumbres M, Klann E
  Learn Memory 20, 11-20.
• Robust mitotic entry is ensured by a latching switch.(2013)
  Tuck C, Zhang T, Potapova T, Malumbres M, Novák B.
  Biol Open 2, 924-931.
• Novel functions of FoxM1: from molecular mechanisms to cancer therapy.(2013)
  Alvarez-Fernández M, Medema RH
  Front Oncol 5, 30-.
• MicroRNA-203: tumor suppression and beyond.(2013)
  Michel CI, Malumbres M
  MicroRNA 2, 118-126.