Moffitt researchers discover pathway critical to lymphoma development

Newswise — Tampa, Florida — MYC protein is a key regulator of cancer cell growth, proliferation, and metabolism through its ability to increase the expression of proteins involved in these processes. Deregulation of the MYC protein occurs in more than half of all cancers and is associated with poor patient prognosis and outcome. Many researchers have devoted considerable effort to targeting the MYC protein as a therapeutic approach to treat cancer. However, this has been very difficult to date and other complementary strategies are being investigated.

and Brand new In the discovery of hematological cancers announced at the same time as the presentation at the 2023 American Annual Meeting of Cancer Research, Moffitt Cancer Center Researchers have shown a possible alternative approach. They showed that MYC activated a downstream pathway that chemically modifies a protein called eIF5A and inhibited this modification process, thereby preventing lymphoma development and progression in a mouse model.

“Our team hypothesized that rather than targeting MYC directly, we might be able to inhibit its cancer effects by targeting proteins downstream of MYC effector proteins that are also important for cancer development. The author and research scientist of Department of Tumor Biology at Moffitt. “We focused on the polyamine biosynthetic pathway, which is involved in cell proliferation and survival and is aberrantly altered in many cancers.”

The Moffitt team showed that MYC induces the expression of eIF5A and an enzyme called DHPS that modifies eIF5A with a unique amino acid called hypusine. Moffitt’s researchers wanted to test whether this chemical modification of eIF5A was important for lymphoma development and maintenance. They performed laboratory experiments using cell lines and mouse models and confirmed that hypusine-modified eIF5A is critical for the development of MYC-regulated lymphoma. When the researchers genetically or chemically blocked this modification by targeting his eIF5A or DHPS, lymphoma development and progression were suppressed. Mechanistically, they found that hypusine-modified eIF5A is important for the production of proteins involved in cell proliferation and DNA replication. This is the first study to conclusively demonstrate that this modification is important for cancer development.

“Since activation of the hypusine cycle is a hallmark of MYC-driven tumors, the development of improved small-molecule inhibitors of DHPS, or agents that bind and block eIF5A-hypusine function, will translate these findings into the clinic.” It is an attractive therapeutic strategy for Dr. John ClevelandMoffitt’s Center Director and Chief Scientific Officer.

This study was supported by the Coltner Couch Endowed Chair for Cancer Research and funding from the National Cancer Institute (CA100603, CA241713, DK124906, DK060581 and P30 CA076292), University of South Florida School of Medicine, Center for Diabetes Research (P30 DK020595). Supported. Florida.

About Moffitt Cancer Center
Moffitt We are dedicated to our life-saving mission to contribute to the prevention and treatment of cancer. The Tampa-based facility is one of only 53 facilities. National Cancer Center Designated Comprehensive Cancer Center, an award that recognizes Moffitt’s scientific excellence, interdisciplinary research, and robust training and teaching. Moffitt’s professional nursing staff is recognized by the American Nurses Credentialing Center for its highest honor, her Magnet® status. With more than 7,800 team members, Moffitt is responsible for her $2.4 billion economic impact across the state. For more information, call 1-888-MOFFITT (1-888-663-3488). MOFFITT.orgfollow the momentum Facebook, twitter, Instagram and Youtube.

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