Scientists have found a gene that plays a central role in the development of melanoma

The mechanisms underlying melanoma, the most aggressive skin cancer, are largely unknown, and despite many years of intensive research, no effective methods of its treatment have been found. Swiss scientists have found a gene that plays a central role in the development of melanoma. Suppression of this gene in mice inhibits the proliferation of tumor stem cells and prevents their survival - an opening that can pave the way for more effective methods of treating this terrible tumor.

Until recently, it was believed that the tumor consists of a set of identical cells, each of which, uncontrolled multiplying, brings an equal contribution to its growth. However, according to a later hypothesis, the tumor can consist of cancer stem cells and other, less aggressive tumor cells. Cancer stem cells can divide in the same way as normal stem cells responsible for the formation of organs, and differentiate into other cells, which means that eventually the tumor is formed from cells that are at different stages of differentiation. Thus, effective therapy of tumors involves, first of all, the fight against cancer stem cells. Proceeding from this, a group of scientists at the University of Zurich studying stem cells, under the guidance of Professor Dr. Lukas Sommer, decided to find out whether the mechanisms important for normal stem cells play the same role in cancer stem cells.

The mechanisms underlying the most aggressive skin cancer - melanoma, are largely unknown, and there are no effective methods for treating it. On a mouse model of a giant congenital nevus and melanoma, Swiss scientists have shown that the nevus and melanoma actively express Sox10, a transcription factor that is crucial for the formation of melanocytes from neural crest cells. Surprisingly, the haploinsufficiency of Sox10 counteracts the formation of NrasQ61K-induced congenital nevus and melanoma without affecting the physiological functions of the neural crest derivatives in the skin. In addition, Sox10 is critical for the preservation of tumor cells in vivo. In humans, almost all congenital nevuses and melanomas Sox10-positive. Moreover, the silencing of Sox10 in human melanoma cells suppresses the properties of neural crest stem cells, inhibits proliferation and cell survival, and completely suppresses the formation of tumors in vivo. Thus, Sox10 is a promising target for the treatment of congenital nevus and human melanoma.

Melanoma cells are malignant skin pigment cells of melanocytes, which originate from the stem cells of the so-called neural crest and are formed during embryonic development. Professor Sommer's group, working closely with dermatologists and pathologists, set out to find the answer to the question of whether there are cells in the human tumor tissue with the characteristics of these specific stem cells.

"As we were able to prove on the basis of analysis of numerous biopsy specimens of tissues of patients with melanoma, this is really so," says Professor Sommer. In particular, one gene that effectively controls the program of these stem cells was highly active in all studied tumor tissues. This gene, known as Sox10, is important for the proliferation and survival of stem cells.

The next step of the Zurich researchers was to test how the Sox10 gene works in human melanoma cells. They found that in cancer cells this gene also controls the program of stem cells and is necessary for their division. To confirm these data on the living body, the researchers turned to the mouse model of melanoma - transgenic animals with genetic mutations similar to those found in human melanoma cells in which such tumors develop spontaneously. It's amazing, but silencing Sox10 in such mice completely suppressed the formation and spread of cancer.

"Our research shows that the tumor can probably be treated by attacking its stem cells," Professor Sommer concludes.

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