• The study identifies the gene Prrx1 as a key regulator of metastatic potential in breast cancer tumors.
• This work, published in Nature Communications, opens new avenues for identifying tumors with a high risk of developing metastases and may improve the classification of breast cancer patients.

Photo: From left to right and top to bottom: the researchers from IN CSIC-UMH Joan Galcerán, Berta L. Sánchez-Laorden, Khalil Kass Youssef, Raúl Jiménez Castaño, Ángela Nieto, and Nitin Narwade. Source: IN CSIC-UMH

Understanding which cells within a tumor will go on to form metastases remains one of the major challenges in cancer research. A study led by the Cell Plasticity in Development and Disease laboratory, headed by Ángela Nieto at the Institute for Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University (UMH) of Elche, offers an unexpected answer: the cells that will give rise to metastases can already be identified within the primary tumor.

The study, published in Nature Communications, combines the analysis of a mouse model of breast cancer with patient data. The results show that, at the invasive front of the tumor, there is a specific population of cells capable of both invading and either proliferating or entering a dormant state. This balance determines whether cells that escape the tumor can initiate new tumor growths in distant organs, the feared metastases.

Nieto’s team has been studying the epithelial-to-mesenchymal transition (EMT) for decades, a program that controls cell migration during embryonic development and is reactivated in tumors to enable cancer cells to spread and form metastases. In this new study, the researchers go a step further by showing that metastatic ability does not arise randomly and is not exclusively driven by the microenvironment of the target organ. Instead, metastatic potential is already determined within a subset of cells present in the primary tumor, which adopt a highly metastatic state orchestrated by a key factor: the Prrx1 gene.

A key regulator of metastasis

According to Raúl Jiménez Castaño, first author of the study, the Prrx1 gene acts as a true master regulator of tumor behavior. “We recently discovered that Prrx1 is crucial for cancer dissemination, and thanks to this work, we now know that it not only activates the programs that allow cells to detach from the primary tumor, but also controls their ability to proliferate and form metastases or enter a dormant state that can last for years”, he explains.

“What is most striking is that the levels of Prrx1 determine its effect on cancer cells”, adds Nieto. This finding helps explain a paradox observed in many tumors: highly invasive cells do not always give rise to metastases, and highly proliferative cells also tend not to spread.

Image of a mouse breast tumor showing distinct cellular populations (cancer cells in pink). Advanced spatial biology technologies enable the simultaneous identification of all cell types present in the tissue. Source: IN CSIC-UMH.

“Without Prrx1, cells do not disseminate; at very high levels, they spread massively but lose the ability to seed and grow in other organs. Only at intermediate levels do they achieve an optimal balance between mobility and growth”, explains the researcher. In these conditions, cells combine invasiveness and proliferation, making them the most dangerous from a clinical perspective.

To reach these conclusions, the team combined mouse genetic models, single-cell analyses, chromatin studies, and spatial transcriptomics techniques that allow researchers to observe the organization and behavior of cells directly within the tumor tissue. The processing and analysis of the large datasets generated from thousands of cells was led by bioinformatics expert from Nieto’s team, researcher Nitin Narwade. In addition, in collaboration with Professor Gema Moreno Bueno from the Universidad Autónoma de Madrid and the MD Anderson Cancer Center Spain Foundation, the researchers analyzed breast cancer patient samples and detected similar patterns of Prrx1 expression, suggesting that the mechanism described could have direct relevance for tumor classification and clinical prognosis.

Taken together, the findings provide new insights into the origin of metastatic potential and open the door to developing strategies to prevent tumor cells from reaching this particularly dangerous state. They also provide a framework for improving patient stratification by identifying markers that predict the risk of metastasis.

A hormetic transcriptional program coregulates invasion, proliferation and dormancy to define metastatic potential. Jiménez-Castaño, R., Narwade, N., Moreno-Bueno, G., Sánchez-Laorden, B., Galcerán, J., Youssef, K.K. and Nieto, M.A. Nature Communications (2026) 17, 3425.

DOI: https://doi.org/10.1038/s41467-026-70242-4

This work was made possible thanks to funding from the State Research Agency – Ministry of Science, Innovation and Universities, the Severo Ochoa Programme for Centres of Excellence, the Spanish Association Against Cancer (AECC), the PROMETEO Programme of the Generalitat Valenciana, and the Momentum Programme of the Spanish National Research Council (CSIC).

Source: Institute for Neurosciences CSIC-UMH (in.comunicacion@umh.es)

La entrada A new study reveals that primary breast tumors already harbor cells with metastatic potential se publicó primero en Instituto de Neurociencias de Alicante.

The Institute for Neurosciences, a joint center of the Miguel Hernández University of Elche (UMH) and the Spanish National Research Council (CSIC), will hold a tribute event in memory of Professor Jorge Manzanares Robles. The event will take place on 23 April at 12:00 at the Assembly Hall of the Institute for Neurosciences (Santiago Ramón y Cajal Building, UMH Sant Joan d’Alacant campus) and will be open to the public until full capacity is reached.

Jorge Manzanares was an internationally renowned researcher in the field of neuropharmacology and a highly regarded figure at the Institute for Neurosciences, where he led the Translational Neuropsychopharmacology of Neurological and Psychiatric Diseases Laboratory. A Professor of Pharmacology and long-serving Dean of the Faculty of Pharmacy at UMH, he also stood out for his dedication to teaching and his commitment to the academic community, leaving a profound mark both scientifically and institutionally, as well as on a personal level.

The event will include contributions from institutional representatives and individuals from Professor Manzanares’ closest circle, including the leadership of the Institute for Neurosciences, the Faculty of Pharmacy at UMH, the Rectorate, as well as family members and colleagues from his research team.

The obituary in his memory, prepared by members of his closest scientific circle, is available for consultation in the attached document (file pdf).

La entrada Memorial service for Prof. Jorge Manzanares, April 23 2026 se publicó primero en Instituto de Neurociencias de Alicante.

Paula Tris,  a PhD student under Prof. Antoni Llobet and Dr. Marcos Gil Sepulcre’s supervision, has successfully defended her thesis today entitled Molecular Catalysts Anchored on Metal Oxides for Artificial Photosynthesis.

The members of the evaluation committee have been: Dr. Olaf Rüdiger (Max-Planck-Institut für Chemische Energiekonversion, Germany); Dr. Pablo Garrido Barros (Universidad de Granada, Spain) and Prof. Nuria Romero  (Centre National de la Recherche Scientifique, France)

First, we will know more about yourself: where are you from, where and what you studied, your hobbies, and any other information you would like to include. 

I am from Zaragoza, a beautiful city in the interior of Spain. I completed my Bachelor’s degree in Chemistry at the University of Zaragoza and later pursued a Master’s degree in Synthesis, Catalysis and Molecular Design at the URV. 

In my free time, I enjoy travelling, hiking, playing guitar, walking my dog on the beach and spending time with friends on a sunny terrace. 

What is your thesis about? 

The development of molecular hybrid materials for (photo)electrochemical water oxidation.   

What triggered your interest for the subject of your thesis? 

 I love nature and spending time outdoors, and I am very concerned about the environment and the challenges we are facing nowadays. Therefore, contributing to the development of sustainable technologies is something that really motivates me. 

The thing that I like most about my thesis is…. 

That I have had the opportunity to learn from many different areas, such as (photo)electrochemistry, spectroscopy synthesis or materials science. I love learning new things, and this is what has kept me motivated through my PhD journey. 

What will you miss the most from ICIQ? 

 ICIQ is a unique place to do research. From an academic point of view, the amount of facilities and the support of all the experienced people working across the different units make it possible to conduct high-quality research. 

From a personal perspective, I will really miss the opportunity to meet people from all over the world and learn about different cultures and traditions. It is a very dynamic environment where there is always someone willing to organize plans, share experiences and make the most of the time together. 

If you were a piece of lab equipment, what would you be? 

I would be a lab bench. I have spent a large part of my PhD there, doing electrochemistry and preparing samples. It’s where you stay connected with your lab mates, share ideas and have those spontaneous discussions that often lead to new insights. It’s also where many funny moments happen, which makes the lab environment more enjoyable.  

La entrada ¡Felicidades, Dra. Tris! se publicó primero en ICIQ.

ICIQ hosted the kick-off meeting of MAGNESIS on 16 April 2026, bringing together the four principal investigators and their teams to launch this new ERC Synergy project.

With a total budget of more than €12 million, MAGNESIS will investigate how applied magnetic fields affect the mechanism of electrochemical reactions, investigating the effects on water oxidation and carbon dioxide reduction, two key reactions in the production of renewable fuels and chemicals.

The project follows an interdisciplinary approach, since no single discipline can address the complexity of spin dynamics, electronic states, charge transfer and interfacial structure on its own. Over the next six years, the consortium will combine electrocatalysis, advanced surface science, magnetism and multiscale computational modelling.

These areas are covered by the complementary expertise of the four leading researchers involved in the initiative: Prof. José Ramón Galán-Mascarós (ICIQ), who coordinates the project and leads the electrochemical work; Prof. Jeppe V. Lauritsen (Aarhus University), responsible for surface science studies; Prof. David Écija (IMDEA Nanociencia), focusing on magnetics characterization at the nanoscale; and Prof. Karsten Reuter (Fritz Haber Institute of the Max Planck Society), who will develop theoretical and computational models.

During the meeting, the team presented their institutions and outlined how their complementary strengths converge to establish the foundations of magneto-electrocatalysis. The scientific session focused on reviewing the recent achievements in the field and preliminary results to set the first steps of the project, including initial plans and key questions to be addressed in the coming months. ICIQ’s coordination team also introduced the project’s governance structure, covering management procedures, financial and reporting timelines, dissemination activities and data management requirements in line with ERC and Horizon Europe guidelines.

The meeting also included a visit to ICIQ’s laboratories and research infrastructure, giving the consortium an opportunity to explore the facilities that will support MAGNESIS throughout its development. Overall, this first meeting was an excellent opportunity for all the teams to establish the master lines for effective collaboration.

Read more about the project here and at magnesis.eu. 

About ERC Synergy Grants 

ERC Synergy Grants support projects of up to €10 million over six years, with an additional €4 million available for start-up costs, major equipment, or access to large research facilities. These grants fund ambitious collaborative projects that require the combined expertise of teams of two to four researchers to address complex scientific challenges. 

In total, 712 proposals were submitted to the call in 2025. Only about one in ten proposals were selected for funding, with the successful projects receiving on average €10.3 million each. The selected projects will be carried out at universities and research centres in 26 countries across Europe and beyond.

Funded by the European Union (ERC 101224406-MAGNESIS).

La entrada MAGNESIS ERC Synergy project holds kick-off meeting at ICIQ se publicó primero en ICIQ.

Michael Reth is a leading German biologist and immunologist and Professor of Molecular Immunology at the University of Freiburg since 1995. His research focuses on the structure and activation of the B cell antigen receptor (BCR), which is essential for antibody production. He discovered the BCR signaling subunits CD79a and CD79b and identified with the immunoreceptor tyrosine-based activation motif (ITAM), a protein sequence motif that is essential for the signal transduction of immunoreceptors on B, T, and mast cells. Since the success of the ITAM identification he has been a motif hunter. During his seminar at the CNIC he described his recent discovery, namely that of the ICOM. The “immunoreceptor coupling and organization motif” short ICOM is a protein motif that is found within the transmembrane domains of many immunoreceptors. Although hidden in the lipid bilayer of the plasma membrane this motif plays an essential role in the regulation of the activity and lateral interaction of many receptors on the surface of immune cells.

Reth has received major awards, including the Gottfried Wilhelm Leibniz Prize and the Paul Ehrlich y Ludwig Darmstaedter, Prize, and is a member of the U.S. National Academy of Sciences, EMBO , and the Leopoldina. His recent work using cryo-electron microscopy to resolve the IgM-type BCR structure (published in Nature, 2022) has important implications for vaccine design.

• If you have to explain what immunology research is to the general public, how do you explain how important it is for us?

Immunology developed in a different way from other sciences. Normally, science begins with curiosity: people ask questions, experiments are designed, answers are found, and new questions arise. From this process, science develops. Later, applications appear. In physics, for example, basic research came first, and only afterwards were machines, radars, and other technologies developed.

In immunology, the process was reversed. People began vaccinating without understanding the mechanisms. For example, scientists like Louis Pasteur and Robert Koch observed that microorganisms can cause diseases and found ways to generate vaccines from them. They vaccinated people and achieved protection, even without knowing how it worked. The application—vaccination—came before the explanation.

This led to a key question: how does it work? The answer began with the discovery of antibodies, molecules in the blood that recognize foreign substances. Antibodies are essential components of the immune system and can be generated through an infection or a vaccination. Vaccines activate not only T cells but also B cells with the appropriate (cognate) BCR, which then differentiate into antibody producing plasma cells.

I started my scientific career when the hybridoma technique was developed. After an anti-virus vaccination, the body produces many different antibodies against a virus. The hybridoma technique allows to immortalize B cells that produce so called monoclonal antibodies with only one specificity. This method, invented by the Nobel laureates César Milstein and, my mentor in Freiburg, Georges Köhler, revolutionized medicine.

Monoclonal antibodies are now widely used in medical therapies and diagnosis. They allow very precise detection of pathogens. However, the mechanisms of B cell activation remained less well understood.

B lymphocytes initially carry BCR complexes on their surface but do not yet produce antibodies. After vaccination, for example, with the spike protein of SARS-CoV-2, only those few B cells that carry a SARS spike-binding BCR on their surface, are activated, proliferate, and differentiate into anti-spike antibody-producing cells. My research focused on understanding the structure of the BCR and how its function on the B cell surface.

• You mentioned something surprising: vaccines were used before understanding how they work. Could this be dangerous for people who distrust vaccines?

This is simply how immunology developed historically, when vaccines were applied without knowing the details of how the immune system works inside the body.

Yet, despite the lack of knowledge people benefited from vaccination and vaccines helped control diseases effectively.

• During the COVID pandemic many people questioned whether new vaccines worked.

 Vaccine development has improved significantly. The polio vaccination is a clear example of one of the most successful medical interventions. In the 1930s and 40s, polio caused widespread fear. Many infected children became paralyzed or could not breathe. The vaccination of all children eliminated that fear and saved lives. The oral polio vaccine, administered on a sugar cube, was simple and effective.

Today, vaccines are rigorously tested and controlled. Although people respond differently due to biological variability, the benefits are clear. Without vaccines, infectious agents would cause far greater harm. Yet more detailed knowledge of the function of the BCR on the B cell surface is required to improve vaccination protocols and to prevent autoimmune diseases.

•  You began your career in the early 1980s. What is the most important discovery about the immune system during your career?

At that time, scientists did not understand how B cells could generate such a diversity. Millions of B cells are continuously produced in the bone marrow, each with a different BCR. The diversity mechanism was finally explained through advances in molecular biology. Antibody genes are assembled from gene segments through a process called V(D)J recombination, generating enormous diversity. This discovery earned Susumu Tonegawa the Nobel Prize.
My research addressed a different question: how B cells are activated. I discovered that the membrane-bound immunoglobulin on the B cell surface is associated with two additional proteins that together form the BCR. The binding of a cognate antigen to this BCR complex triggers intracellular signaling and activates the expansion and differentiation of B cell to antibody producing plasma cells.
A more profound knowledge of BCR signaling is also relevant for a better treatment of cancer diseases such as leukemia and lymphomas. These B-cell tumors are driven by a deregulated BCR signal. Some viruses can also transform B cells and induce tumor formation through similar mechanisms.

• With this knowledge, immunotherapy has advanced significantly. Could it be a universal solution for diseases?

There have been major successes. Monoclonal antibodies such as Rituximab eliminate B cells by targeting CD20. This therapy is now used in the treatment of severe autoimmune diseases such as multiple sclerosis (MS). However, the anti-CD20 antibody therapy also removes healthy B cells, leading to temporary immune deficiency. Our recent research (described in a manuscript that is just been accepted for publication in EMBO Journal) has shown that CD20 plays a role in keeping B cells in a resting state. This illustrates how scientific understanding evolves: therapies may exist before their mechanisms are fully understood but a better understanding can then improve the therapies.

• You mentioned at the beginning that you are a motif hunter and that, as a dyslexic scientist, you have the advantage to recognize patterns in protein sequences where other people only see letters.

Yes, for a long time dyslexia was regarded as a neurological disorder of children who fail to easily attain the skills of reading and writing. Such children were often counter selected by the school system and prevented from obtaining a higher education. For me this was particularly bad, as the German school system in the 1950s was run by teachers that grew up with an ideology favoring the elimination of the unfit. It was only due to my father, who did not accept the verdict, that his son was an idiot, that I managed to survive this system and finally could study biology.

Newer research now suggests that dyslexia is not at all a disorder but a specialization in exploration, that was selected during human evolution. People with dyslexia (and these can be up to 10-20% of a population) are specialized to explore the unknown and this can play a fundamental role in human adaptation to changing environments. Thus, without dyslexic people and their explorative hunter and gatherer skills, humanity would not have survived tough times during the last 300.000 years of its evolution. But then 5.000 years ago with the advent of written languages and their importance for cultural development, brains with rapid automated processing skills had an advantage over explorative brains and the readers and writers were the winners of this development. However, now with the help of computers and AI tools, explorative brains may play again an important role in human evolution if we manage not to destroy our planet during this time. I am approaching the end of my scientific career but I think my recent ICOM discovery will be an important contribution for the better understanding of immunological and other receptors of the cell surface and the regulation of the immune system in health and disease once it becomes accepted.

Un descubrimiento del Grupo de Transformación y Metástasis del Centro Nacional de Investigaciones Oncológicas (CNIO) abre una vía hacia la identificación de las lesiones precancerosas de mama que se convertirán en tumores. Este trabajo, dirigido por Eva González Suárez, se publica en la revista Nature Communications.

La investigación se ha centrado en el papel de la proteína RANK, cuya intervención en la génesis de los tumores de mama fue descubierta por la propia González-Suárez en el año 2010 en el Instituto de Investigación Biomédica Bellvitge (IDIBELL), donde mantiene una línea de investigación clínica.

En el tejido mamario conviven dos tipos de células: las luminales, que producen la leche; y las basales, que son contráctiles y permiten la expulsión de esa leche. Varios estudios sugerían que los tumores de mama se originan exclusivamente en una subpoblación de células luminales, las llamadas progenitoras luminales.

El trabajo que ahora se publica, con Jaime Redondo-Pedraza como primer autor, desvela en cambio que los tumores pueden empezar en otro tipo de células, a las que los autores denominan células infieles y que derivan de las células basales.

 Las células ‘infieles’ en que empieza el cáncer

La nueva investigación muestra que la expresión de la proteína RANK en las células basales hace que pierdan su identidad, y se conviertan en nuevas células que no son claramente ni basales ni luminales, sino híbridas, con características de ambas. Estas son las células infieles.

En las células infieles comenzarían todos los tipos de tumores de mama, tanto los luminales, que expresan receptores hormonales (+), como los “triples negativos” que no los expresan (-).

“Lo que sabemos ahora es que las células basales de la mama pueden dar lugar a todos los tipos de tumores” –explica Eva González–. “Podríamos decir que la identidad definida de las células protege de la aparición tumoral. Sin embargo, cuando las células pierden su identidad inicial y se convierten en esas células híbridas o infieles, provengan de dónde provengan, es cuando dan lugar a la aparición del cáncer”.

Firma genética en las lesiones que progresarán a cáncer

El grupo ha desarrollado una firma genética, que detecta en el origen de las lesiones precancerosas esas células infieles, lo que permite identificar cuáles de ellas van a evolucionar hacia tumores invasivos.

Tras su trabajo de identificación de la firma genética en ratones, el grupo de Eva González Suárez ha probado este nuevo marcador con una cohorte de lesiones precancerosas mamarias humanas y han comprobado que es capaz de identificar aquellas lesiones que sí se convertirán en cáncer.

“Un diagnóstico frecuente en mama es el del carcinoma ductal in situ, que es una lesión considerada precancerosa de la que hasta ahora no podía saberse si iba o no a evolucionar hacia un cáncer”, señala González-Suárez. “Como eso hasta el momento no podía saberse, se trata a todas las mujeres a las que se les diagnostica esas lesiones como si ya fuera un cáncer. Es decir, se está sobretratando a un número muy alto de mujeres”.

Los diagnósticos de esas lesiones precancerosas han aumentado gracias a los programas de cribado y la mejora de las técnicas de imagen, hasta el punto de que en este momento el 20% de todos los diagnósticos de cáncer son esas lesiones precancerosas que, en realidad, no son cáncer. De ellas solo un 30% se convertirán en cáncer, pero la imposibilidad de saber cuáles ha hecho que la inmensa mayoría se traten como cánceres.

La firma genética identificada por el grupo de Eva González podría detectar las lesiones precancerosas que van a evolucionar hacia tumores invasivos, es decir, hacia el cáncer.

“Ahora hay que confirmar la firma con una cohorte independiente, y refinarla para poder utilizarse en la clínica para identificar las lesiones que sí se convertirán en cáncer invasivo”, afirma González.

Entidades financiadoras:

Consejo Europeo de Investigación (ERC); Comunidad Autónoma de Madrid; Fundación «la Caixa», Ministerio de Ciencia, Innovación y Universidades a través de la Agencia Estatal de Investigación.

Sobre el Centro Nacional de Investigaciones Oncológicas (CNIO)

El Centro Nacional de Investigaciones Oncológicas (CNIO) es un centro público de investigación dependiente del Ministerio de Ciencia, Innovación y Universidades. Es el mayor centro de investigación en cáncer en España y uno de los más importantes en Europa. Integra a medio millar de científicos y científicas, más el personal de apoyo, que trabajan para mejorar la prevención, el diagnóstico y el tratamiento del cáncer.

La entrada Un grupo del CNIO avanza en la identificación de las lesiones que se convertirán en cáncer de mama, lo que podrá ayudar a evitar el sobretratamiento se publicó primero en CNIO.