Robert Kypta
rkypta
Robert Kypta
ASSOCIATE PRINCIPAL INVESTIGATOR
Cancer Heterogeneity Lab
Email: rkypta@cicbiogune.es
Phone: 4210 / 944 061 322
Address: Bizkaia Science and Technology Park, building 801A, Derio (Bizkaia)

Robert Kypta was an undergraduate at Oxford University and carried out his PhD at EMBL in Heidelberg, where he studied signaling by Src family tyrosine kinases and PDGF. After postdoctoral training in Louis Reichardt’s lab at the University of California San Francisco, where he found an association between the cadherin-catenin complex and receptor tyrosine phosphatases, he set up his own lab as a Wellcome Trust Career Development Fellow at the MRC Laboratory for Molecular Cell Biology, UCL, focusing on catenin function in neuroblastoma and colorectal cancer. He then moved to Imperial College as a Lecturer, where his group focused on Wnt signaling in prostate cancer. In 2005, he set up his lab at CIC bioGUNE, where his goal is to develop new therapies by targeting signals that determine tumor and stem cell fate. His research has resulted in several awards, including an ARTP Prize and an Androgens Meeting Prize.

Latest Publications
Intravital imaging of Wnt/?-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis
Stoletov, K;Sanchez, S;Gorrono, I;Rabano, M;Vivanco, MDM;Kypta, R;Lewis, JD
JOURNAL OF CELL SCIENCE
2023-02-01

2022

Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment
Al Shareef, Z;Ershaid, MNA;Mudhafar, R;Soliman, SSM;Kypta, RM
CANCERS
2022-12-01
Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease
Lewis, A;Sanchez, S;Berti, G;Pan-Castillo, B;Nijhuis, A;Mehta, S;Eleid, L;Gordon, H;Gadhok, R;Kimberley, C;Minicozzi, A;Chin-Aleong, J;Feakins, R;Kypta, R;Lindsay, JO;Silver, A
CLINICAL SCIENCE
2022-11-01

2021

Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
Spethmann, T;Bockelmann, LC;Labitzky, V;Ahlers, AK;Schroder-Schwarz, J;Bonk, S;Simon, R;Sauter, G;Huland, H;Kypta, R;Schumacher, U;Lange, T
MOLECULAR ONCOLOGY
2021-02-17

2019

Wnt-11 as a Potential Prognostic Biomarker and Therapeutic Target in Colorectal Cancer
Gorrono-Etxebarria, I;Aguirre, U;Sanchez, S;Gonzalez, N;Escobar, A;Zabalza, I;Quintana, JM;Vivanco, MD;Waxman, J;Kypta, RM
CANCERS
2019-06-26
The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3K4me3 Mark
Ormaza, G;Rodriguez, JA;de Opakua, AI;Merino, N;Villate, M;Gorrono, I;Rabano, M;Palmero, I;Vilaseca, M;Kypta, R;Vivanco, MDM;Rojas, AL;Blanco, FJ
JOURNAL OF MOLECULAR BIOLOGY
2019-05-31
A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells
Domenici, G;Aurrekoetxea-Rodriguez, I;Simoes, BM;Rabano, M;Lee, SY;San Millan, J;Comaills, V;Oliemuller, E;Lopez-Ruiz, JA;Zabalza, I;Howard, BA;Kypta, RM;Vivanco, MD
ONCOGENE
2019-04-25

2018

In Silico Approach for Immunohistochemical Evaluation of a Cytoplasmic Marker in Breast Cancer
Mazo, C;Orue-Etxebarria, E;Zabalza, I;Vivanco, MDM;Kypta, RM;Beristain, A
CANCERS
2018-12-15
Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1
Al Shareef, Z;Kardooni, H;Murillo-Garzon, V;Domenici, G;Stylianakis, E;Steel, JH;Rabano, M;Gorrono-Etxebarria, I;Zabalza, I;Vivanco, MD;Waxman, J;Kypta, RM
ONCOGENE
2018-09-27
CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-beta Signaling in Prostate Cancer
Kardooni, H;Gonzalez-Gualda, E;Stylianakis, E;Saffaran, S;Waxman, J;Kypta, RM
CANCERS
2018-06-01
Frizzled-8 integrates Wnt-11 and transforming growth factor-beta signaling in prostate cancer
Murillo-Garzon, V;Gorrono-Etxebarria, I;Akerfelt, M;Puustinen, MC;Sistonen, L;Nees, M;Carton, J;Waxman, J;Kypta, RM
NATURE COMMUNICATIONS
2018-05-01
Proteomic Studies Reveal Disrupted in Schizophrenia 1 as a Player in Both Neurodevelopment and Synaptic Function
Ramos, A;Rodriguez-Seoane, C;Rosa, I;Gorrono-Etxebarria, I;Alonso, J;Veiga, S;Korth, C;Kypta, RM;Garcia, A;Requena, JR
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2018-01-29

2017

WNT signalling in prostate cancer
Murillo-Garzon, V;Kypta, R
NATURE REVIEWS. UROLOGY
2017-11-01
Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells
Bengoa-Vergniory, N;Gorrono-Etxebarria, I;Lopez-Sanchez, I;Marra, M;Di Chiaro, P;Kypta, R
MOLECULAR NEUROBIOLOGY
2017-10-01

2016

Dickkopf-3 regulates prostate epithelial cell acinar morphogenesis and prostate cancer cell invasion by limiting TGF-beta-dependent activation of matrix metalloproteases
Romero, D;Al-Shareef, Z;Gorrono-Etxebarria, I;Atkins, S;Turrell, F;Chhetri, J;Bengoa-Vergniory, N;Zenzmaier, C;Berger, P;Waxman, J;Kypta, R
CARCINOGENESIS
2016-01-01
The stem cell cocktail: neural reprogramming just got easier.
Bengoa-Vergniory, N (Bengoa-Vergniory, Nora );Kypta, R (Kypta, Robert )
STEM CELL INVESTIGATION
2016-01-01

2015

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells
Bengoa-Vergniory, N;Kypta, RM
CELLULAR AND MOLECULAR LIFE SCIENCES : CMLS
2015-11-01

2014

Dickkopf-3 Alters the Morphological Response to Retinoic Acid During Neuronal Differentiation of Human Embryonal Carcinoma Cells
Alfonso, RJ;Gorrono-Etxebarria, I;Rabano, M;Vivanco, MD;Kypta, R
DEVELOPMENTAL NEUROBIOLOGY
2014-12-01
A Switch From Canonical to Noncanonical Wnt Signaling Mediates Early Differentiation of Human Neural Stem Cells
Bengoa-Vergniory, N;Gorrono-Etxebarria, I;Gonzalez-Salazar, I;Kypta, RM
STEM CELLS
2014-12-01
A screen for transcription factor targets of Glycogen Synthase Kinase-3 highlights an inverse correlation of NF kappa B and Androgen Receptor Signaling in Prostate Cancer
Campa, VM;Baltziskueta, E;Bengoa-Vergniory, N;Gorrono-Etxebarria, I;Wesolowski, R;Waxman, J;Kypta, RM
ONCOTARGET
2014-09-30
MT5-MMP regulates adult neural stem cell functional quiescence through the cleavage of N-cadherin
Porlan, E;Marti-Prado, B;Morante-Redolat, JM;Consiglio, A;Delgado, AC;Kypta, R;Lopez-Otin, C;Kirstein, M;Farinas, I
NATURE CELL BIOLOGY
2014-07-01
Sox2 promotes tamoxifen resistance in breast cancer cells
Piva, M;Domenici, G;Iriondo, O;Rabano, M;Simoes, BM;Comaills, V;Barredo, I;Lopez-Ruiz, JA;Zabalza, I;Kypta, R;Vivanco, MDM
EMBO MOLECULAR MEDICINE
2014-01-01

2013

Downregulation of Dickkopf-3 disrupts prostate acinar morphogenesis through TGF-beta/Smad signalling
Romero, D;Kawano, Y;Bengoa, N;Walker, MM;Maltry, N;Niehrs, C;Waxman, J;Kypta, R
JOURNAL OF CELL SCIENCE
2013-04-15

2012

Distinct expression and activity of GSK-3 alpha and GSK-3 beta in prostate cancer
Darrington, RS;Campa, VM;Walker, MM;Bengoa-Vergniory, N;Gorrono-Etxebarria, I;Uysal-Onganer, P;Kawano, Y;Waxman, J;Kypta, RM
INTERNATIONAL JOURNAL OF CANCER
2012-09-15
Wnt/beta-catenin signalling in prostate cancer
Kypta, RM;Waxman, J
NATURE REVIEWS UROLOGY
2012-08-01
Wnt11 in 2011-the regulation and function of a non-canonical Wnt
Uysal-Onganer, P;Kypta, RM
ACTA PHYSIOLOGICA
2012-01-01

2011

Issues associated with the use of phosphospecific antibodies to localise active and inactive pools of GSK-3 in cells
Campa, VM;Kypta, RM
BIOLOGY DIRECT
2011-01-24
Distinct Roles for Wnt-4 and Wnt-11 During Retinoic Acid-Induced Neuronal Differentiation
Elizalde, C;Campa, VM;Caro, M;Schlangen, K;Aransay, AM;dM Vivanco, M;Kypta, RM
STEM CELLS
2011-01-01

2010

The neuron-specific isoform of glycogen synthase kinase-3 beta is required for axon growth
Castano, Z;Gordon-Weeks, PR;Kypta, RM
JOURNAL OF NEUROCHEMISTRY
2010-04-01
Mechano-transduction in Osteoblastic Cells Involves Strain-regulated Estrogen Receptor alpha-mediated Control of Insulin-like Growth Factor (IGF) I Receptor Sensitivity to Ambient IGF, Leading to Phosphatidylinositol 3-Kinase/AKT-dependent Wnt/LRP5 Receptor-independent Activation of beta-Catenin Signaling
Sunters, A;Armstrong, VJ;Zaman, G;Kypta, RM;Kawano, Y;Lanyon, LE;Price, JS
JOURNAL OF BIOLOGICAL CHEMISTRY
2010-03-19
Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells
Uysal-Onganer, P;Kawano, Y;Caro, M;Walker, MM;Diez, S;Darrington, RS;Waxman, J;Kypta, RM
MOLECULAR CANCER
2010-03-10

2009

Secreted Frizzled-related protein-1 is a negative regulator of androgen receptor activity in prostate cancer
Kawano, Y;Diez, S;Uysal-Onganer, P;Darrington, RS;Waxman, J;Kypta, RM
BRITISH JOURNAL OF CANCER
2009-03-31

2006

Regulation of prostate cell growth and morphogenesis by Dickkopf-3
Kawano, Y;Kitaoka, M;Hamada, Y;Walker, MM;Waxman, J;Kypta, RM
ONCOGENE
2006-10-19

2005

GSK-3 inhibitors and their potential in the treatment of Alzheimer's disease
Kypta, RM
EXPERT OPINION ON THERAPEUTIC PATENTS
2005-10-01

The Cancer Heterogeneity Lab seeks to understand tumor heterogeneity and use this knowledge to deliver new approaches to treatment of patients. Breast cancer is a particularly heterogeneous disease. The identification and characterization of cells with stem-like properties (cancer stem/progenitor cells, CSCs) in breast cancer has opened new possibilities for anti-cancer therapies. Furthermore, CSCs have been implicated in tumor initiation and resistance to current treatments, including hormone therapy. In addition, characterization of the regulation of normal epithelial cell differentiation is fundamental to understanding breast cancer heterogeneity.

A major objective of the laboratory is to gain further insight into the roles of steroid hormone receptors in normal breast tissue and during breast cancer development. Thus, the influences of hormones, other signaling factors and the microenvironment on breast stem cells and on their transformation into cancer initiating cells are being explored, particularly focusing on their effects during development of resistance to hormone therapy. Recent work from the lab has revealed the role of CSCs in resistance to tamoxifen and has highlighted the molecular heterogeneity observed in response to the cell environment. Presently, studies are in progress to improve further our knowledge of the molecular mechanisms regulating stem and cancer stem cells with the final aims of (1) identifying biomarkers of resistance to therapy and (2) progressing our understanding of breast cancer biology. Recent studies have focused on the transcription factors SOX2 and SOX9, which play key roles in CSCs in many tumor types.

The group also maintains a strong interest in secreted factors whose expression is altered in metastatic and treatment-resistant disease, such as Wnt-11, which is found upregulated in prostate and colorectal cancers. We identified FZD8 as a major Wnt-11 receptor in prostate cancer that integrates Wnt and TGF-beta signals and we have developed Wnt-11 function-blocking antibody nanoparticles, in collaboration with A. Cortajarena at CIC biomaGUNE. In addition, we study Dkk-3, which regulates the tumor microenvironment. We have identified Dkk-3 effectors and are using epigenetic approaches to restore Dkk-3 levels expression in cancer, in collaboration with colleagues at Imperial College London.

Latest Publications

Intravital imaging of Wnt/?-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis

Stoletov, K;Sanchez, S;Gorrono, I;Rabano, M;Vivanco, MDM;Kypta, R;Lewis, JD

JOURNAL OF CELL SCIENCE

2023-02-01

Comparison of Genomic Profiling Data with Clinical Parameters: Implications for Breast Cancer Prognosis

Lopez-Ruiz, JA;Mieza, JA;Zabalza, I;Vivanco, MDM

CANCERS

2022-09-01

Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity

Parra-Perez, AM;Perez-Jimenez, A;Gris-Cardenas, I;Bonel-Perez, GC;Carrasco-Diaz, LM;Mokhtari, K;Garcia-Salguero, L;Lupianez, JA;Rufino-Palomares, EE

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

2022-07-01

Substrate stiffness modulates the viscoelastic properties of MCF-7 cells

Gil-Redondo, JC;Weber, A;Zbiral, B;Vivanco, MD;Toca-Herrera, JL

JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS

2022-01-01

Single-Crystal-to-Single-Crystal Cluster Transformation in a Microporous Molybdoarsenate(V)-Metalorganic Framework

Dissem, N;Artetxe, B;San Felices, L;Beobide, G;Castillo, O;Ruiz-Bilbao, E;Lezama, L;Vivanco, MD;Haddad, A;Gutierrez-Zorrilla, JM

INORGANIC CHEMISTRY

2021-10-04

Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development

Font-Diaz, J;Jimenez-Panizo, A;Caelles, C;Vivanco, MD;Perez, P;Aranda, A;Estebanez-Perpina, E;Castrillo, A;Ricote, M;Valledor, AF

SEMINARS IN CANCER BIOLOGY

2021-08-01

Estrogen Modulates Epithelial Breast Cancer Cell Mechanics and Cell-to-Cell Contacts

Zbiral, B;Weber, A;Iturri, J;Vivanco, MDM;Toca-Herrera, JL

MATERIALS

2021-06-01

SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

Oliemuller, E;Newman, R;Tsang, SM;Foe, S;Muirhead, G;Noor, F;Haider, S;Aurrekoetxea-Rodriguez, I;Vivanco, MD;Howard, BA

ELIFE

2020-09-10

OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models

Fabre, M;Ferrer, C;Dominguez-Hormaetxe, S;Bockorny, B;Murias, L;Seifert, O;Eisler, SA;Kontermann, RE;Pfizenmaier, K;Lee, SY;Vivanco, MD;Lopez-Casas, PP;Perea, S;Abbas, M;Richter, W;Simon, L;Hidalgo, ...

CLINICAL CANCER RESEARCH

2020-07-01

The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development

Qureshi, R;Picon-Ruiz, M;Aurrekoetxea-Rodriguez, I;de Paiva, VN;D'Amico, M;Yoon, H;Radhakrishnan, R;Morata-Tarifa, C;Ince, T;Lippman, ME;Thaller, SR;Rodgers, SE;Kesmodel, S;Vivanco, MD;Slingerland, ...

CELL METABOLISM

2020-06-02