Researchers have discovered a new enzyme that may be relevant to the development of toxins and other pharmacological targets for drug resistance in human cells.
Along with lead author of the study, Dr. Harlan Krumholz from UT Health San Antonio’s Oswaldo Cruz Research Institute (LOCTR), University of Texas MD Anderson Cancer Center (UofMC), and University of California San Diego (UCSF), the study was published in the Journal of Functional Products.
Combining fluorescence imaging with advanced cryo-electron microscopy, the team detected two enzymes, ORXO-MIRO and SFMT2, that appeared to operate as ligands for an essential brain pathway. These enzymes targeted mammalian target of rapamycin (mTOR) which, in turn, are impaired in lung cancer and other cancers.
As recently reported in Toxins, mTOR is a signaling pathway through which cancer cells send signals to other cancer cells to grow. This is the first demonstration that commensal cells, cells that should not differ from other types of cells such as human blood cells, tend to become cancerous.
About 25 percent of all lung cancer cases are caused by mutations in SNB2 proteins (SNB2s) that cause leukemia, lymphoma or other neoplasms of the blood of people with immune systems called lymphoblasts. Interactions between parasitic cells and mTOR family members, and their genetic cousins, are central to tumor growth.
Scientists have identified the production process of mTOR as an important player in controlling and diminishing tumor growth. MTOR inhibitors have been developed for several diseases due to their ability to erode drug resistance.
Until now, no enzyme has been discovered that saw only mutation in fox-pioneer proteins.
Viviane Lerche, a UT Health San Antonio researcher of Cancer Research and Development.
A team of collaborators at Fred Hutchinson Cancer Research Center (FRC) in Seattle/King County, where Lerche is an affiliate of, tested whether a new enzyme, known as PGR1b or pGR1b inhibitors, could selectively target SNB2s. They found that these enzymes were effective in selectively targeting SNB2s and also showed potent anticancer activity in lab dishes.
“Using a novel approach that involved the use of nanoparticles, we were able to delay the activated enzyme and reveal our discoveries and gain an unprecedented level of specificity and efficacy,” Lee J. Wu, Ph.D., co-lead investigator of the study and the Kin-Cheng Jin of UT Health San Antonio Department of Chemistry and Biochemistry, said. “This enabled us to chemically destroy the enzymes’ target protein. After that, we monitored the chemical reactions of the enzyme protected by the nanoparticles.”