Grupo Pedro Jaén doctors Luis Ríos and Pedro Jaén took part in an international study led by the Université libre de Bruxelles investigating how loss of FAT1 activity may promote metastasis.
The journal Nature published an international research study involving the Ramón y Cajal Institute for Health Research and, specifically, members of its Dermatology Research Group, including Dr Luis Ríos Buceta and Dr Pedro Jaén, who at the time were consultant dermatologist and Head of the Dermatology Department at Ramón y Cajal University Hospital, respectively.
Both specialists collaborated in an international study led by the Université libre de Bruxelles and involving clinical and research departments in Belgium, France and Spain. The findings provided new insights into mechanisms involved in tumour progression and may have future implications for the development of more personalised cancer treatments.
The role of the FAT1 gene in metastasis
Using mouse and cellular models of squamous cell carcinoma, the researchers investigated the role of FAT1, a tumour suppressor gene that is frequently mutated in several types of cancer. The study found that loss of FAT1 activity promoted changes associated with tumour progression, metastatic potential and treatment resistance in the experimental models analysed.
Metastasis occurs when tumour cells spread from the primary tumour and establish secondary tumours in other parts of the body. This process involves multiple biological steps, including changes that allow tumour cells to detach, migrate, enter the blood or lymphatic circulation and colonise distant tissues.
One of the processes involved in tumour cell plasticity is known as the epithelial-to-mesenchymal transition (EMT). The researchers found that loss of FAT1 function promoted a hybrid EMT state, together with increased tumour stemness and metastatic behaviour. These findings suggest that alterations in FAT1 can influence biological pathways associated with a more invasive tumour phenotype.
In the experimental models studied, FAT1 loss promoted characteristics associated with metastasis and more aggressive tumour behaviour.
Beyond skin cancer
These findings may be relevant to several types of cancer, not only skin cancer, the field most closely related to our work at Grupo Pedro Jaén (Go to Skin Cancer Unit).
Squamous cells are present in different epithelial tissues throughout the body, and squamous cell carcinomas can arise in areas including the skin, lungs, head and neck, oral cavity and other organs.
For this reason, the biological mechanisms identified in the study may have relevance beyond cutaneous squamous cell carcinoma. However, further research is required to determine how these experimental findings translate into prognosis and treatment decisions in patients with different types of cancer.
Implications for treatment
The study also investigated the relationship between FAT1 alterations and response to different treatments. “We discovered that cancers with FAT1 mutations are highly resistant to drugs, including the EGFR inhibitors most commonly used in patients with metastatic carcinomas,” explained Professor Cédric Blanpain, a researcher at the Université libre de Bruxelles and one of the study authors.
In the experimental models analysed, tumours with FAT1 loss also showed increased sensitivity to SRC kinase inhibitors, a class of drugs already used in the treatment of certain haematological malignancies. These findings raise the possibility that, in the future, the molecular characteristics of a tumour — including alterations affecting FAT1 — could help identify therapeutic vulnerabilities and guide more personalised treatment strategies.
However, the results were derived primarily from preclinical models. Further studies in patients are required before FAT1 status can be used routinely to select treatments or predict clinical response. The importance of this research therefore lies both in improving our understanding of the molecular mechanisms involved in metastasis and in identifying potential therapeutic pathways that could be investigated in future clinical studies.
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Authorship and references
The content of this article has been prepared by the Grupo Pedro Jaén Communications Department and Medical Team in accordance with our editorial commitment, which ensures the accuracy and regular updating of the information provided.
References:
1. Pastushenko I, Mauri F, Song Y, et al. Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis. Nature. 2021;589:448–455. doi:10.1038/s41586-020-03046-1. https://doi.org/10.1038/s41586-020-03046-1.
