Hebrew University Discovery Could Lead to New Cancer Treatments

Discovery expected to facilitate the development of new treatment methods that could prevent the spread of cancerous growths.

Dan Even
Dan Even
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Dan Even
Dan Even

Researchers at the Hebrew University of Jerusalem have discovered a new pathway by which cells in the body become cancerous. The discovery is expected to facilitate the development of new treatment methods that could block this process and prevent the spread of cancerous growths as well as new diagnostic tools to distinguish between normal and malignant tumors.

In their article in the scientific journal "Cell Reports," the researchers describe a gene found in every cell of the body that manufactures an enzyme called S6K1. This enzyme appears in two forms, one long and one short. It is the latter variant of the enzyme, which like all enzymes is a protein, that is involved in the process of tumor formation.

While the long variant of the S6K1 enzyme is composed of more than 500 different amino acids, the short form contains only 300. In the article, "S6K1 Alternative Splicing Modulates Its Oncogenic Activity and Regulates mTORC1," the short variation, or isoform, of the protein is described for the first time. Healthy cells contain a relatively small number of this form of S6K1, which the researchers discovered encourages nearby cells to become cancerous. The research team, led by Ph.D. candidate Vered Ben-Hur and adviser Dr. Rotem Karni of the Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, demonstrated that an additional protein found in the body, SRSF1, depresses the activity of the long variation of S6K1 and activates its short form - the one implicated in the cancer process.

The short variation of S6K1 activates the signaling pathway between cells. This pathway encourages nearby cells to divide in an unregulated manner and thereby become cancerous, spreading and invading various tissues within the body.

The researchers identified the short variform of S6K1 first in mice and then in cell cultures taken from women with breast cancer. They later found significant levels of the short variation in cultures taken from people with lung cancer and from people with cancer of the colon. "We found that the pathway we have described is very important and that it takes place in nearly all types of cancerous tumors," Karni said.

In a related discovery, the researchers found that in laboratory conditions the long variation of S6K1 actually depresses tumor activity and even prevents healthy cells from becoming cancerous, just the reverse of the effect of this enzyme's short version. "We showed that the [S6K1] protein causes damage when it is truncated, whereas damage to the long form could actually intensify the disease," Karni explained.

The researchers have not yet identified the environmental factors affecting the production of either the short or the long variations of the S6K1 enzyme, but the assumption is that environmental factors that have been associated with the development of cancer, such as prolonged exposure to sun or to known carcinogens, could accelerate the production of the short form. Further study will be needed to test this hypothesis.

The research team is now working on turning the short form of S6K1 into its long form and then testing whether this could prevent or at least slow the growth of cancerous tumors.

"We are developing materials that could switch off the splicing mechanism in order to create more of the long form of the protein and fewer of the short ones," Karni said, adding, "Today we can do this in the laboratory, and the intention is to develop a drug therapy based on this discovery."

The team has already determined that new cancer drugs, recently approved for use in Europe, can affect the activity of the short form of S6K1.

Hadassah University Hospital, Mt. Scopus.Credit: Yael Engelhart

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