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Thursday, December 08, 2022

Health News | Scientists Discover Cancer Triggers That May Stimulate Targeted Drug Therapies | Lately

Washington [US]July 10 (ANI): Researchers have definitively linked the function of a specific domain of important proteins in the biology of plant microbes to a trigger of cancer in humans, knowledge that has eluded scientists for decades.

The team’s findings, published in Nature Communications Biology, open a new avenue for the development of selective drug therapies to fight a variety of cancers, such as those that start in the breast and stomach.

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ORNL scientists have set out to experimentally prove what they first deduced with computational studies: that the plasminogen-apple-nematode, or PAN, domain is linked to cell proliferation that drives tumor growth in humans and defense signaling during plant-microbe interactions in bioenergy crops. The association was first made when researchers explored the genomes of crops such as poplar and willow.

In the most recent study, the ORNL team identified four central amino acids called cysteine ​​residues in the HGF protein critical for PAN domain function and studied their behavior in human cancer cell lines. They found that mutating any of these amino acids turned off the signaling pathway known as HGF-c-MET, which is abnormally increased in cancer cells, causing them to multiply and spread rapidly.

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Because cysteine ​​residues are known to have many functions, the scientists also randomly tested other cysteines throughout the protein and found that none of them had the same impact on turning off HGF-c-MET signaling. The mutation of the four key cysteines had no effect on the overall structure of the protein and only inhibited the cancer signaling pathway, the team noted in the study.

Disrupting the right signal is one of the biggest challenges in developing new cancer therapies, said ORNL geneticist Wellington Muchero.

“It’s very difficult to design molecules to interfere with an entire protein,” he said. “Knowing the specific amino acids to target within this protein is a huge step forward. You don’t have to search the entire protein; you just look for those four specific residues.”

The identification of these core residues is a testament to the predictive power the team built at ORNL, leveraging the lab’s expertise in plant biology and biochemistry, genetics, and computational biology, as well as its supercomputing capabilities and the CRISPR/CAS-9 gene analysis tool. edition.

The discovery could lead to treatments for other diseases, including disrupting the infection pathway in mosquitoes to make them less able to carry the malaria parasite and fighting the HLB virus by killing citrus trees in Florida and California by targeting the citrus psyllid insect. Asian who spreads it. .

In plants, ORNL scientists are using their knowledge of the PAN domain to improve resistance to pathogens and pests in biomass crops such as poplar and willow, which can be broken down and converted into sustainable jet fuel. They are exploring the genetic processes that encourage beneficial interactions between plants and microbes to build resistance in these crops.

The research demonstrates the similarities in the DNA structure of plants, humans and other organisms, which makes plants an important discovery platform, Muchero said. “We can do things with plants that you can’t do with humans or animals in the research process,” he added.

“I can work with equal efficiency on plant and human cancers. The experience is the same,” said Debjani Pal, a postdoctoral researcher at ORNL with a background in biochemistry and human cancer research. “We’ve established a global experimental platform here at ORNL that shows, no matter what system you’re using, plant or animal, if your hypothesis is correct, then the science can be repeated in all of them, no matter what cell line you’re using. .”

“At the bottom of it all, we have the same biological underpinnings,” Muchero said. (ANI)

(This is an unedited and auto-generated story from the syndicated news feed, the LatestLY team may not have modified or edited the body of content)

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