A new mouse model developed by researchers at the Journal of Investigative Dermatology traces a rare and aggressive skin cancer to hair follicle cells. The finding could reshape how scientists study and treat Merkel cell carcinoma.
A single-cell layer in the skin, pressed close to the base of hair follicles, may hold the origin story of one of the rarest and most aggressive skin cancers known to medicine.
Merkel cell carcinoma is a neuroendocrine skin cancer with a poor prognosis and, until recently, an unclear starting point. According to research published in the Journal of Investigative Dermatology, scientists have developed a mouse model that traces the cancer's beginnings to SOX9-expressing hair follicle cells — a specific population of Merkel cell progenitors sitting within the hair follicle.
The study found that most Merkel cell carcinoma tumours carry monoclonal integration of Merkel cell polyomavirus DNA. The virus expresses two proteins — small T antigen and large T antigen — that the researchers identified as the primary drivers of tumour development. What remained poorly understood was how, exactly, those viral proteins transformed healthy cells into cancerous ones.
Building on earlier work that identified SOX9-positive hair follicle cells as susceptible to viral reprogramming, the team introduced small T antigen expression alongside reduced activity of the Trp53 gene — a known tumour suppressor — specifically in those SOX9-positive cells. The result, according to the study, was the development of metastatic neuroendocrine tumours whose histopathological and immunophenotypic features closely matched those seen in human Merkel cell carcinoma.
The researchers described the absence of a physiologically relevant in vivo model as a longstanding barrier to understanding the disease. This mouse model, they said, addresses that gap directly.
Why this matters for skin cancer research
Merkel cell carcinoma is more likely to affect people with compromised immune systems and those with significant cumulative sun exposure — including people with albinism, whose skin produces little to no melanin to filter ultraviolet radiation. The condition is rare in the general population, but its aggressive progression and high metastatic rate make early biological understanding critical.
The study does not address albinism directly. But the finding that a specific progenitor cell population in the hair follicle can be reprogrammed into a fast-spreading tumour adds a precise new piece to a long-incomplete picture of how UV-related and virus-associated skin cancers begin.
Researchers now have a replicable biological system, the study noted, in which to test interventions at the earliest stages of tumour formation — before the cancer metastasises and treatment options narrow.
The work was published in the Journal of Investigative Dermatology. The study's authors did not specify a clinical timeline for translating the model's findings into human treatment protocols.
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