Fox Chase Researchers Find NeuroD1 Protein Determines Cell Differentiation in Medulloblastoma

PHILADELPHIA (July 29, 2020)—Researchers at Fox Chase Cancer Center have determined that the protein NeuroD1 promotes cell differentiation in medulloblastoma, a finding that could help researchers develop novel cancer treatments.

Although it is rare, medulloblastoma is the most common type of malignant brain tumor found in children. It starts in the cerebellum and can spread to other parts of the brain through cerebrospinal fluid. The tumor can affect a patient’s movement, balance, and muscle coordination.

The study was led by Yan Cheng, a master’s student at Fox Chase working in the lab of Zeng-Jie Yang, MD, PhD, associate professor in the Cancer Signaling and Epigenetics Program. Other researchers from Fox Chase, other research centers in the United States, and China participated in the study as well.

“Instead of killing a tumor by toxic drugs, which is widely used now, we provided evidence that we can also treat a tumor by inducing them to differentiate,” said Yang.

“After many studies, we see that in many ways the tumor cells behave similarly to the normal cell progenitors. So after issuing several papers showing this, we decided to try to stop tumor cell proliferation by inducing them to differentiate into mature neurons,” he said. A progenitor is a cell with a tendency to differentiate or mature into a specific kind of cell.

Yang said this method would be most beneficial to medulloblastoma patients because treatments such as chemotherapy often have side effects that affect development, leaving children diagnosed with these tumors most vulnerable.

Once they differentiate, medulloblastoma cells permanently lose their potential to form tumors and their capacity to quickly multiply. The differentiation of medulloblastoma is driven by the protein NeuroD1. However, the expression of NeuroD1 in most medulloblastoma cells is repressed by trimethylation of the enzyme histone 3 lysine-27. Histone methylation is the modification of amino acids in a histone protein by adding one, two, or three methyl groups.

When histone lysine methyltransferase is inhibited, it prevents histone 3 lysine-27 trimethylation, resulting in increased NeuroD1 expression and enhanced differentiation in medulloblastoma cells. This increased differentiation of tumor cells consequently reduces tumor growth, according to the authors.

Yang said the study illuminates some of the mechanisms of medulloblastoma formation and can help provide possible treatments that would spare normal cells.

“Next, we will change gears and study another tumor that occurs in the brain and spinal cord called glioma. We’ll be investigating how to induce the differentiation of glioma cells for the same purpose,” said Yang.

The study, “NeuroD1 Dictates the Differentiation of Medulloblastoma,” was published in Cell Reports.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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