Parkin protein tied to Parkinson’s disease aids anti-tumor responses

25 September 2024

A scientist looks through a microscope on a table with a beaker and test tubes.

Parkin, a protein linked to Parkinson’s disease that’s lost in certain types of cancer, triggers the release of signaling molecules that activate and attract immune cells to fight tumors, according to a study led by researchers at The Wistar Institute in Philadelphia.

“Parkin has only recently been implicated for its role in cancer, so our study adds to the knowledge base being formed around that role. We are the first to demonstrate its dual role in suppressing tumor traits while activating innate immunity,” Dario C. Altieri, MD, president and CEO of The Wistar Institute, said in a press release.

The study, “Parkin activates innate immunity and promotes anti-tumor immune responses,” was published in The Journal of Clinical Investigation by Altieri and an international team of researchers.

“Whether these findings can be extended beyond tumor responses … is presently unknown,” the researchers wrote. “However, it should be noted that defective innate immunity and failure to achieve pathogen clearance are also important drivers of neuroinflammation and [Parkinson’s].”

Parkin helps break down damaged or excess proteins in cells. In Parkinson’s, mutations in the gene that codes for Parkin, PRKN, result in a faulty version of the protein being produced that leads to the buildup of toxic forms of dopamine and other molecules damaging to nerve cells.

However, Parkin can also be silenced, that is, turned off, in some types of cancer, such as lung, ovarian, and breast cancer, by epigenetics. Epigenetics is like a cellular “light switch” that can turn genes on or off without changing the underlying DNA code. It uses chemical markers, like methyl groups, to wrap the DNA more tightly, which makes it harder for the cell to access certain genes, effectively turning them off.

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Parkin’s role in cancer growth

To better understand the role of Parkin in cancer, the researchers began by turning the PRKN gene back on in tumor cells. When Parkin was restored, it triggered the tumor cells to produce interferons, which are proteins that help the immune system respond to pathogens, or disease-causing microorganisms, and other threats, like cancer.

Testing this in mice by using decitabine, an anti-cancer medication that removes the methyl groups from DNA, allowed PRKN to be active again. When the gene was reactivated, cancer growth slowed down.

Parkin triggered the release of interferons, which brought immune cells called T-cells into close contact with the cancer to attack the tumor cells. When researchers blocked interferon signaling in mice, tumor cells continued to grow in number even if Parkin was present, showing the immune response is needed for Parkin to stop cancer growth.

“A role of Parkin in immune modulation and enhanced T-cell effector functions carries important implications for the [disease-causing mechanisms] of cancer and other conditions, including the response to infectious pathogens and Parkinson’s disease,” the researchers wrote.

The post Parkin protein tied to Parkinson’s disease aids anti-tumor responses appeared first on Parkinson's News Today.

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