Each cell in the body follows a strict protocol for manufacturing the proteins it needs to function.
A cell's identity depends on the levels of proteins it produces, and these can be altered by changes in the way proteins are translated from genetic instructions.Each cell in the body follows a strict protocol for manufacturing the proteins it needs to function. When a cell turns cancerous, however, its protein production goes off script. A new study led by researchers at The Rockefeller University takes a close look at one way in which this procedure goes haywire in skin cells as they turn cancerous.
‘One way in which the protein production goes haywire in skin cells as they turn cancerous has been studied by researchers at The Rockefeller University.’
Senior author Elaine Fuchs, the Rebecca C. Lancefield Professor and head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, said, "Changes in translation appear to be particularly important as
normal stem cells become malignant, and our new experiments detail the
control mechanisms behind a shift that occurs just prior to the
development of skin cancer," adds Fuchs, who is a Howard Hughes Medical
Institute investigator. The research, which identifies a potential avenue for future cancer treatments, was described in Nature.
In order to function, cells need to turn instructions encoded in their DNA into protein. They do so in two major steps: first, DNA is transcribed into a molecule called messenger RNA, which is then translated into protein. Certain cancerous tumors are known to contain an unusual ratio of protein to messenger RNA, however, which suggests translation is altered in cancer.
Using mice, the team explored changes in translation that occur as the animals develop a common type of skin cancer called squamous cell carcinoma. Adapting a technique developed for cultured cells in co-author Jonathan Weissman's lab at the University of California, San Francisco, they captured messenger RNA as it was being translated within skin stem cells in mice. These molecules were collected from both normal skin stem cells and those primed to become malignant.
Within the pre-malignant cells, the researchers found decreases in regular protein production as well as an uptick in tumor-promoting proteins. Ataman Sendoel, a postdoc in the Fuchs lab and first author on the study, traced this shift back to a change in the proteins that kick off the process of translation. In regular skin cells, eIF2 has this job; in the soon-to-be cancerous cells, he found that eIF2 was inactivated, and its relative, eIF2A, had taken over.
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The team's work suggests eIF2A could potentially provide a therapeutic target for new cancer treatments, and the researchers have begun investigating this possibility with help from a grant from the Robertson Therapeutic Development Fund.
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Source-Eurekalert