by King’s College London

Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-56299-7

New research published in Nature Communications reveals how cancer cells are altered by their surroundings, enabling them to change their shape and break out of a tumor. The discovery, which is the culmination of almost a decade of research that began at King’s, paves the way for treatments that will tackle cancer before it can spread.

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Tumors are held together by a structure called the extracellular matrix (ECM) that acts like the scaffolding around a building under construction.

A team from The Institute of Cancer Research London, led by Professor Victoria Sanz Moreno (formerly of King’s), and Barts Cancer Institute at Queen Mary University of London (BCI-QMUL), discovered how cancer cells use the layout of this scaffolding structure as a “roadmap” to leave the tumor. They found that the ECM triggers changes within the cancer cells themselves—altering their shape and boosting their ability to travel to different parts of the body.

This breakthrough means that aggressive tumors that are likely to metastasize can now more easily be identified at an earlier stage—allowing clinicians to tailor treatment sooner. Drugs are currently in development to target the ECM’s layout, as well as the genes that drive these cell shape changes—which could stop cancer in its tracks before it can escape the tumor and spread.

The team, working in the Breast Cancer Now Toby Robins Research Center at The Institute of Cancer Research (ICR), looked at tumor tissue from 99 patients with melanoma skin cancer and breast cancer.

They saw that the ECM was laid out differently in three distinct areas of the tumor. Like scaffolding, the ECM is made up of a number of components, including pole-like fibers. At the center of the tumor, the fibers were spread out and disorganized, while at the border they were tightly packed and thicker.

At the outermost border of the tumor, the fibers were arranged pointing away from the tumor—providing the “tracks” for the cancer cells to follow as they escape from the tumor. At this outermost border of the tumor, the cancer cells were rounded—a more invasive cell shape.

The team tested whether the conditions at the border of the tumor make the cancer cells more aggressive. They grew melanoma cancer cells in a model of these conditions and injected them into mice. Cancer cells grown in these conditions were more likely to spread to the lungs and metastasize than melanoma cells grown in control conditions with disorganized fibers.

The researchers saw differences in the type of genes present in the cells depending on where in the tumor they came from. Cells at the border of the tumor had more genes linked to cell migration, rounding of the cell shape, and inflammation—all making the cells more aggressive and likely to survive.

The team also saw an increase in the expression of genes for enzymes that impact the organization of the matrix—highlighting how cancer cells corrupt their surroundings to break out of the tumor.

Comparing these findings to cancers from patients with 14 different tumor types, including melanoma, breast, pancreatic, lung cancer and glioblastoma—an aggressive brain cancer—the researchers found that a higher presence of these genes was associated with a shorter survival time.

The researchers say that these findings open new avenues for treatment to tackle cancer before it can spread, such as drugs targeting lysyl oxidase (LOX), which are already in clinical trials for other conditions. These drugs work by targeting an enzyme that stabilizes the matrix, which is found more abundantly in the border region of tumors. The ICR has previously carried out research to show the possibility of targeting LOX in cancer treatment.

“Our research has uncovered the roadmap that cancer cells follow to break out of a tumor, enabling it to cause a secondary tumor elsewhere in the body. Now that we understand this roadmap, we can look to target different aspects of it, to stop aggressive cancers from spreading,” says Professor Victoria Sanz Moreno, professor of cancer cell and metastasis biology at The Institute of Cancer Research, London.

“The fibers in the structure surrounding the tumor are denser and are laid out like a path for cells to follow, the further out at the border of the tumor that we look. Future research should explore ways to target this arrangement, to prevent cancer cells from being able to escape and follow this path. We may also find that targeting this dense arrangement of fibers means other drugs can reach cancer cells more easily, which could improve how well treatments work.”

More information: Oscar Maiques et al, Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis, Nature Communications (2025). DOI: 10.1038/s41467-025-56299-7

Journal information:Nature Communications

Provided by King’s College London

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