Revealing the role of key genes in cancer "immortality"
2022-11-15
Researchers from the University of Pittsburgh School of Medicine found the missing "puzzle" in the mystery of how melanoma controls its mortality. In a paper in the latest Science magazine, Dr. Jonathan Alder's team described how tumors use gene changes to promote explosive growth and prevent self destruction. This discovery may change the way oncologists understand and treat melanoma. In healthy cells, telomeres shorten as cells divide. Interruptions in the maintenance of its length may lead to serious disease. Short telomere syndrome can lead to premature aging and death, but long telomeres are associated with cancer. Telomerase protein is responsible for prolonging telomere, protecting telomere from damage and preventing cell death. Mutations that contribute to cell immortality are crucial to the development of tumors, and many types of malignant tumors use mutations in the telomerase gene TERT to activate this protein, so that cells can continue to grow and achieve immortality. Melanoma is particularly notorious. About 75% of melanoma tumors contain TERT gene mutations, which stimulate protein production and increase telomerase activity. However, when scientists mutate TERT in melanocytes, they cannot produce the same long telomeres as in patients' tumors. Facts show that mutation of TERT promoter is only "half the story". Therefore, the researchers determined to find the link between melanoma, TERT promoter mutation and long telomere deletion. Previously, researchers found a region in a telomere binding protein called TPP1, which often mutates in melanoma. The study found that the mutation in TPP1 was strikingly similar to TERT. They are located in the newly annotated TPP1 promoter region and stimulate protein production. When the researchers added the mutated TERT and TPP1 back to the cells, the two proteins worked together to produce the long telomeres unique to melanoma tumors. TPP1 is a missing factor that scientists have been looking for for a long time, and it has been hidden in people's eyes. This discovery has changed the way scientists understand the pathogenesis of melanoma, but it also has the potential to improve treatment. By identifying the unique telomere maintenance system of cancer, scientists have new therapeutic goals. (Outlook New Times)
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