Study Uncovers New Aspect of Ewing Sarcoma

LAWRENCE – A team of University of Kansas researchers are helping uncover hidden aspects of Ewing Sarcoma which may lead to the discovery of new cancer treatments.

Mizuki Azuma, an associate professor of Molecular Biosciences at the University of Kansas, sought to go beyond the well-studied aspect of fusion protein in Ewing Sarcoma, and instead turned her attention toward an additional genetic abnormality in the cancer.

Working with Haeyoung Kim (Ph.D. Candidate), Hyewon Park (Research Assistant), Evan T Schulz (Ph.D. Candidate), and Yoshiaki Azuma (Professor), the team found that the reduction of EWS proteins in a cell causes abnormal cell division, which results in a daughter cell that has abnormal copy numbers of DNA.

In a healthy cell, the EWS gene encodes a multifunctional protein that is involved in gene expression, cell signaling, and RNA processing and transport. This DNA is known to be mutated in a rare type of childhood cancer, Ewing Sarcoma, that occurs in bones or in the soft tissue around the bones. Specifically, the EWS gene is fused to other gene, and one copy of the EWS gene is lost in the patient. The team made cells that mimic the DNA condition of Ewing Sarcoma, and samples were analyzed at the Microscopy and Analytical Imaging Research Resource Core Laboratory (MAI). The team discovered that the EWS normally located at a part of DNA works together with Aurora B (an important protein required for cell division), but reduced EWS induces abnormal copy numbers of DNA due to the failure in the cell division.

Azuma’s findings could lead toward new cancer treatments, as the same process that causes the reduction of the EWS gene in a cell is common across many types of cancer, including other childhood sarcoma, Leukemia, Melanoma, and breast cancer. By pinpointing the cause of abnormal cell division in EWS, it will allow researchers to test for and hopefully find a drug that targets the EWS phenomena, and in turn apply the same drug to cancers with similar factors.

“When you find a particular phenomenon specific to a cancer, it allows you to screen cancer drugs that specifically works only in the phenomenon. In this case, it will allow us to test if cancer drugs will kill the Ewing Sarcoma cells with lower levels of EWS.” Mizuki Azuma said.

The findings have just been published in the paper “EWSR1 prevents the induction of aneuploidy through direct regulation of Aurora B” in the peer-reviewed journal Frontiers in Cell and Developmental Biology. 

The Azuma lab is currently applying for a grant to continue their research as Mizuki Azuma believes, “this research was sort of a baseline study, and we aim to reveal the entire pathway in future study”.

Contact info:

Mizuki Azuma, azumam@ku.edu, The University of Kansas.

Journal

Frontiers in Cell and Developmental Biology

DOI

10.3389/fcell.2023.987153