Researchers discover marker that can indicate when a type of skin cancer is preparing to spread

From left to right: Noemí Haro, Óscar Pozo, Inma Hernández-Muñoz, Evelyn Andrades, Paloma Torres & Ramon Pujol. Credits: Hospital de Mar/IMIM

Cells that form cutaneous squamous cell carcinoma tumors prepare to migrate to the lymph nodes to metastasize to other organs, and they make changes so that they can survive this process. According to a study led by researchers at the Inflammatory and Neoplastic Dermatological Diseases Research Group at the Hospital del Mar Medical Research Institute, published in the journal Life Sciences Alliancethese cells stop consuming glucose so they can survive by using LDL cholesterol molecules, the so-called bad cholesterol. This novel marker may be a promising candidate for lipid metabolism inhibitor treatments that target these cells to prevent metastasis.

Each year in Spain, 74,000 new cases of non-melanoma skin cancer are diagnosed, a group that also includes squamous cell carcinoma, the second most common cancer. The lifetime risk of suffering from this is between 7% and 11% and the incidence has doubled over the past thirty years. In squamous cell carcinoma, approximately 4% of tumors metastasize. And there is no tool to anticipate this. Now, however, the study led by the IMIM-Hospital del Mar provides a marker that indicates which of them are about to migrate to the lymph nodes to reach other organs.

The role of dyskerin

The researchers were able to confirm the role of the protein dyskerin in this process. They did this with samples from 100 primary tumors from patients with squamous cell carcinoma. In those who had metastasized, in vitro tests showed how certain non-coding RNA particles were no longer expressed and how levels of dyskerin, the protein that helps stabilize them, dropped. In other words, these levels indicated that the tumor cells were preparing to migrate.

“This is a mechanism that can explain metastasis, but not only that, it is also a marker of when the tumor cell is preparing to migrate and initiate this process,” explains Dr. Inmaculada Hernández-Muñoz, the study’s principal investigator. .

The drop in dyskerin levels causes a metabolic change in the tumor cells, and they shift from consuming glucose to feeding on lipids, specifically LDL cholesterol molecules, the so-called bad cholesterol. This allows them to survive migration to the lymph nodes and from there to other organs where they multiply. The change is only temporary and they restore their original characteristics when they complete the process. The researchers were able to demonstrate this with markers of lipid metabolism in the samples analysed. This marker was indeed present in the patients with the worst prognosis.

In view of this, Dr. Hernández Muñoz said the study “provides a good model for understanding how tumor cells spread in the early stages of the tumor.” In fact, “It paves the way to investigate whether people with higher levels of LDL cholesterol are also at greater risk of metastases.”

The work also showed how treating the affected cells with statins, which are used to fight high levels of bad cholesterol, reversed lipid metabolism and prevented the onset of metastasis. At the same time, the researchers showed that this mechanism of change in cell metabolism also occurs in other tumor types.

More information:
Evelyn Andrades et al, Loss of dyskerin facilitates the acquisition of metastatic properties by altering the mevalonate pathway, Life Sciences Alliance (2023). DOI: 10.26508/lsa.202201692

Provided by Center for Genomic Regulation

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Researchers discover marker that can indicate when a type of skin cancer is preparing to spread

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