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The work, led by IRB Barcelona, shows that tumours with chromosomal instability can promote their own growth by damaging the surrounding healthy tissues.
Senescent tumour cells release signals that block the proliferation of neighbouring cells, ultimately inducing their death.
Published in EMBO Reports, the study identifies a new interaction mechanism between the tumour and its environment, which could open new avenues for researching targeted therapies against senescent cells.
Chromosomal instability is a common feature in many solid tumours and is associated with greater aggressiveness. For years, its main contribution to cancer was thought to be driving the evolution of tumour genomes, causing cells to gain chromosomes with growth-promoting genes or lose chromosomes with tumour-suppressor genes.
A study led by Dr. Marco Milán’s laboratory at IRB Barcelona shows that chromosomal instability promotes tumour growth through a completely new mechanism. The work, published in EMBO Reports, reveals that tumour cells with an incorrect number of chromosomes can become senescent and release signals that alter the behaviour of neighbouring tissues.
The research, conducted in Drosophila melanogaster, shows that these senescent cells not only promote tumour growth and invasiveness but also induce the death of nearby healthy cells. This, in turn, feeds back into and fuels the tumour's growth.
"What we are seeing is that the tumour doesn't just grow due to its own internal alterations. It also interacts with the surrounding healthy tissue, preventing its cells from proliferating and ultimately killing them. And that process is necessary for the tumour to grow further," explains Dr. Marco Milán, an ICREA researcher and head of the Development and Growth Control laboratory at IRB Barcelona.
Cells that stop dividing but remain active
When a cell has an incorrect number of chromosomes—a condition known as aneuploidy—its internal functioning becomes unbalanced. When cells can no longer manage the accumulated damage properly, they trigger alarm signals. Often, they enter senescence: a state in which they stop dividing, increase in size, and release molecules that influence surrounding cells.
In principle, senescence is a protective mechanism. In specific situations, such as an injury, senescent cells help attract the immune system to repair the tissue. The problem arises when these cells are not cleared and persist in the body chronically. When that happens, their sustained activity can generate inflammation and promote pathological processes, such as ageing or cancer.
In this work, the team studied senescent cells caused by aneuploidy—that is, cells with an abnormal number of chromosomes. Although these cells present highly diverse alterations, the researchers observed that they share a common response. This shared program includes halting cell division, activating stress response mechanisms, and an increased capacity to secrete signals into their environment.
The research was carried out in Drosophila melanogaster, a model that allows scientists to observe in a living organism how cells with chromosomal instability interact with their surrounding tissues. Many of the behaviours described here, such as aneuploidy, senescence, and the secretion of inflammatory signals, have also been observed in mammalian cells.
A tumour that modifies its environment
Dr. Milán’s laboratory has spent more than a decade studying how chromosomal instability contributes to tumour development. Previous work by the group had identified signals secreted by senescent cells that promote tumour growth, invasion, and systemic effects on the body.
In this new study, the team describes a fourth function of these cells: their ability to damage neighbouring healthy tissue. The researchers have identified several molecules secreted by senescent cells that act on nearby normal cells. Some of these molecules, such as Dilp8 (Relaxin in humans) and ImpL2 (IGFBP7 in humans), reduce the proliferation of neighbouring cells. Others, such as the cytokines Upd1 and Upd3 (IL-6 in humans) and Eiger (a molecule equivalent to TNF in mammals), help induce the death of these nearby healthy cells.
"We know that the tumour needs these neighbouring cells to die in order to grow more. What we don't yet know for sure is why. One possibility is that the death of these cells releases nutrients, such as amino acids or other metabolites, which the tumour can then exploit," explains Kaustuv Ghosh, co-first author of the study alongside Aishwarya Kunchur.
Moving forward, the team wants to study the heterogeneity of these aneuploid senescent cells with greater resolution. To do this, "we plan to use single-cell analysis to see if the gain or loss of specific chromosomes is associated with specific behaviours within the tumour," notes Dr. Milán.
This work is part of the doctoral theses of Kaustuv Ghosh and Aishwarya Kunchur, co-first authors of the study, conducted in Dr. Marco Milán's laboratory at IRB Barcelona.
Related article:
A tumour-host feed-forward loop contributes to the growth of chromosomal instability-induced tumours
Kaustuv Ghosh, Aishwarya Kunchur and Marco Milán
EMBO Reports (2026) DOI: 10.1038/s44319-026-00811-7
About IRB Barcelona
The Institute for Research in Biomedicine (IRB Barcelona) pursues a society free of disease. To this end, it conducts multidisciplinary research of excellence to cure cancer and other diseases linked to ageing. It establishes technology transfer agreements with the pharmaceutical industry and major hospitals to bring research results closer to society, and organises a range of science outreach activities to engage the public in an open dialogue. IRB Barcelona is an international centre that hosts 400 researchers and more than 30 nationalities. Recognised as a Severo Ochoa Centre of Excellence since 2011, IRB Barcelona is a CERCA centre and member of the Barcelona Institute of Science and Technology (BIST).
