Living cells constantly recycle receptors, proteins and lipids with a direct impact on nutrient uptake, re-sensitisation to environmental signals, immune surveillance and waste management. Failure to recycle results in reduced signalling, oxidative stress, protein mislocalisation and aggregation, which are pathological hallmarks of many cardiovascular, cancer, and neurodegenerative diseases. Endosomes are key recycling compartments where the biosynthetic and endocytic pathways intersect. Here, the fate of sorting receptors is directly linked to their selective recruitment into tubulo-vesicular carriers. Our understanding of receptor recycling in a motif-dependent manner, the formation of such tubulo-vesicles and the functional components defining their architecture remains very limited. Retromer is a novel protein coat complex with a central role in multiple receptor-sorting events in the endosomes. Retromer combines receptor recruitment with membrane tubulation properties, but unlike other classical coats, it does so through a single-layer or “cage-free” organization.
This laboratory is interested in understanding how retromer components form a coat around tubulo-vesicles, how transmembrane receptors are selectively recruited to control essential cell processes, and how certain pathogens subvert and co-opt these interactions.
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Principal Investigator
Aitor Hierro Ayuela
Ikerbasque Research Professor TECHNICIANS / DOCTORAL CANDIDATES -
Alberto Marina
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Elsa Natividad Astorga Simón
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Marta Pardo Piñón
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David Blázquez Ruano
Members
Latest Publications
Architecture of the ESCPE-1 membrane coat
Lopez-Robles, C; Scaramuzza, S; Astorga-Simon, EN; Ishida, M; Williamson, CD; Baños-Mateos, S; Gil-Carton, D; Romero-Durana, M; Vidaurrazaga, A; Fernandez-Recio, J; Rojas, AL; Bonifacino, JS; ...
NATURE STRUCTURAL & MOLECULAR BIOLOGY
2023-06-15
Editorial: Energy Requirements in Membrane Trafficking
Guardia, CM; Hierro, A; Gershlick, DC;
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
2021-10-14
Structural insight into the membrane targeting domain of theLegionella deAMPylase SidD
Tascón, I; Li, X; Lucas, M; Nelson, D; Vidaurrazaga, A; Lin, YH; Rojas, AL; Hierro, A; Machner, MP;
PLOS PATHOGENS
2020-08-01
VPS29, a tweak tool of endosomal recycling
Baños-Mateos, S; Rojas, AL; Hierro, A;
CURRENT OPINION IN CELL BIOLOGY
2019-08-01
RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases
Lin, YH; Lucas, M; Evans, TR; Abascal-Palacios, G; Doms, AG; Beauchene, NA; Rojas, AL; Hierro, A; Machner, MP;
PLOS PATHOGENS
2018-02-01
Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL
Romano-Moreno, M; Rojas, AL; Williamson, CD; Gershlick, DC; Lucas, M; Isupov, MN; Bonifacino, JS; Machner, MP; Hierro, A;
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2017-12-26
Retromer
Lucas, M; Hierro, A;
CURRENT BIOLOGY
2017-07-24
Structural Mechanism for Cargo Recognition by the Retromer Complex
Lucas, M; Gershlick, DC; Vidaurrazaga, A; Rojas, AL; Bonifacino, JS; Hierro, A;
CELL
2016-12-01
Role of cholesterol in SNARE-mediated trafficking on intracellular membranes
Enrich, C; Rentero, C; Hierro, A; Grewal, T;
JOURNAL OF CELL SCIENCE
2015-03-15
INT CEL MOL BIO
Hierro, A; Gershlick, DC; Rojas, AL; Bonifacino, JS; Jeon, KW;
INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 318
2015-01-01
A molecular mechanism for endosomal avoidance by the pathogen Legionella pneumophila.
Gaspar, A; Lucas, M; Rojas, A; Hierro, A; Machner, M;
MOLECULAR BIOLOGY OF THE CELL
2014-12-01
Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5
Lucas, M; Gaspar, AH; Pallara, C; Rojas, AL; Fernández-Recio, J; Machner, MP; Hierro, A;
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2014-08-26
Structural basis for the wobbler mouse neurodegenerative disorder caused by mutation in the Vps54 subunit of the GARP complex
Pérez-Victoria, FJ; Abascal-Palacios, G; Tascón, I; Kajava, A; Magadán, JG; Pioro, EP; Bonifacino, JS; Hierro, A;
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2010-07-20
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.
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Principal Investigator
María dM Vivanco
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Associate Principal Investigator
Robert Kypta
TECHNICIANS / DOCTORAL CANDIDATES -
Irantzu Gorroño
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Isabel Gris Cardenas
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Virginia Gamboa Aldecoa
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Lorena Fernández de Larrea González
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Miriam Rábano
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Connor Benjamin Parry
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Víctor Manuel Barrios Álvarez
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Ignacio Pachón Bermúdez
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Martín Parga Pazos
Members
Latest Publications
Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research
van Amerongen, R; Bentires-Alj, M; van Boxtel, AL; Clarke, RB; Fre, S; Suarez, EG; Iggo, R; Jechlinger, M; Jonkers, J; Mikkola, ML; Koledova, ZS; Sorlie, T; Vivanco, MD;
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
2023-12-01
Characterization of Breast Cancer Aggressiveness by Cell Mechanics
Zbiral, B; Weber, A; Vivanco, MD; Toca-Herrera, JL;
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2023-08-01
Measuring (biological) materials mechanics with atomic force microscopy. 5. Traction force microscopy (cell traction forces)
Gil-Redondo, JC; Weber, A; Vivanco, MD; Toca-Herrera, JL;
MICROSCOPY RESEARCH AND TECHNIQUE
2023-06-22
Application of self-organizing maps to AFM-based viscoelastic characterization of breast cancer cell mechanics
Weber, A; Vivanco, MDM; Toca-Herrera, JL;
SCIENTIFIC REPORTS
2023-02-22
Application of self-organizing maps to AFM-based viscoelastic characterization of breast cancer cell mechanics
Weber, A; Vivanco, MDM; Toca-Herrera, JL;
Scientific Reports
2023-02-22
Intravital imaging of Wnt/?-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis
Stoletov, K; Sanchez, S; Gorroño, I; Rabano, M; Vivanco, MDM; Kypta, R; Lewis, JD;
JOURNAL OF CELL SCIENCE
2023-02-01
Application of self-organizing maps to AFM-based viscoelastic characterization of breast cancer cell mechanics
Weber, A; Vivanco, MDM; Toca-Herrera, JL;
Scientific Reports
2023-01-16
Comparison of Genomic Profiling Data with Clinical Parameters: Implications for Breast Cancer Prognosis
López-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; Pérez-Jiménez, A; Gris-Cárdenas, I; Bonel-Pérez, GC; Carrasco-Díaz, LM; Mokhtari, K; García-Salguero, L; Lupiáñez, 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
2021-11-23
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; Gutiérrez-Zorrilla, JM;
INORGANIC CHEMISTRY
2021-09-21
Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development
Font-Díaz, J; Jiménez-Panizo, A; Caelles, C; Vivanco, MD; Pérez, P; Aranda, A; Estébanez-Perpiñá, E; Castrillo, A; Ricote, M; Valledor, AF;
SEMINARS IN CANCER BIOLOGY
2021-06-10
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; Domínguez-Hormaetxe, S; Bockorny, B; Murias, L; Seifert, O; Eisler, SA; Kontermann, RE; Pfizenmaier, K; Lee, SY; Vivanco, MD; López-Casas, PP; Perea, S; Abbas, M; Richter, ...
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; DAmico, M; Yoon, H; Radhakrishnan, R; Morata-Tarifa, C; Ince, T; Lippman, ME; Thaller, SR; Rodgers, SE; Kesmodel, S; Vivanco, ...
CELL METABOLISM
2020-06-02
Single-Cell Probe Force Studies to Identify Sox2 Overexpression-Promoted Cell Adhesion in MCF7 Breast Cancer Cells
Iturri, J; Weber, A; Vivanco, MD; Toca-Herrera, JL;
CELLS
2020-04-01
Resveratrol-Induced Temporal Variation in the Mechanical Properties of MCF-7 Breast Cancer Cells Investigated by Atomic Force Microscopy
Iturri, J; Weber, A; Moreno-Cencerrado, A; Vivanco, MD; Benítez, R; Leporatti, S; Toca-Herrera, JL;
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2019-07-01
Wnt-11 as a Potential Prognostic Biomarker and Therapeutic Target in Colorectal Cancer
Gorroño-Etxebarria, I; Aguirre, U; Sanchez, S; González, N; Escobar, A; Zabalza, I; Quintana, JM; Vivanco, MD; Waxman, J; Kypta, RM;
CANCERS
2019-06-26
Chitosan nanogels as nanocarriers of polyoxometalates for breast cancer therapies
Pérez-Alvarez, L; Ruiz-Rubio, L; Artetxe, B; Vivanco, MDM; Gutiérrez-Zorrilla, JM; Vilas-Vilela, JL;
CARBOHYDRATE POLYMERS
2019-06-01