The protein dyskerin may provide important clues as to how cutaneous squamous cell carcinoma tumors prepare themselves to migrate to the lymph nodes to metastasize other organs.

The protein dyskerin may provide important clues as to how cutaneous squamous cell carcinoma tumors prepare themselves to migrate to the lymph nodes to metastasize other organs, a new study suggests.

These cells stop consuming glucose so that they can survive by using LDL cholesterol molecules, the so-called bad cholesterol, and dyskerin may be a promising candidate for treatments involving lipid metabolism inhibitors targeting these cells to prevent metastasis.

In squamous cell carcinoma, around 4% of tumors metastasize. And there is no tool for anticipating this. The new research provides a marker that indicates which of cells are about to start migrating towards the lymph nodes to reach other organs.

The researchers used  samples from a hundred primary tumors from patients with squamous cell carcinoma. In those that had metastasized, in vitro tests showed how certain non-coding RNA particles were no longer expressed and how the levels of dyskerin, which is the protein that helps to stabilize them, decreased. 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 the moment at which the tumor cell is preparing to migrate and initiate this process," explains study author Dr. Inmaculada Hernández-Muñoz, in a news release. She is affiliated with the Inflammatory and Neoplastic Dermatological Diseases Research Group at the Hospital del Mar Medical Research Institute in Barcelona, Spain.

The drop in dyskerin levels induces 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 the migration to the lymph nodes and, from there, to other organs where they proliferate. The change is only temporary, and they recover their original characteristics when they have completed the process. The researchers were able to prove this using lipid metabolism markers in the analyzed samples. This marker was present in the patients with the worst prognosis.

The study "provides a good model for understanding how tumor cells spread in the early stages of the tumor,” says Dr. Hernández Muñoz. "It paves the way for studying whether people with higher levels of LDL cholesterol are also at greater risk of metastasis.”

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

PHOTO IMAGE: FROM LEFT TO RIGHT: NOEMÍ HARO, ÓSCAR POZO, INMA HERNÁNDEZ-MUÑOZ, EVELYN ANDRADES, PALOMA TORRES & RAMON PUJOL 

PHOTO CREDIT: HOSPITAL DE MAR/IMIM