A protein that promotes abnormal growth in melanoma cells has been identified for the first time by a team of researchers led by Emily Bernstein, PhD, Associate Professor of Oncological Sciences, and Dermatology, at the Icahn School of Medicine at Mount Sinai.
The novel discovery that the H2A.Z.2 protein is highly expressed in melanoma, appears to turn on the cell cycle, and makes melanoma cells grow faster, could also lead to therapeutic strategies that serve to inhibit cell proliferation. The results of Dr. Bernstein’s study were published in the July 2, 2015, issue of Molecular Cell.
The incidence of malignant melanoma, the most lethal form of skin cancer, has been rising steadily over the past 30 years, with roughly 73,870 new cases diagnosed annually in the United States, according to the American Cancer Society. While significant advances have been made in immune and targeted therapies in recent years, distinct subsets of patients either do not respond to these treatments or develop resistance over time.
“Ours was the first study to show that H2A.Z.2 drives melanoma progression by affecting chromatin structure and to identify a specific role for H2A.Z.2 in any tumor type,” says Dr. Bernstein. “The next step would be gaining a better understanding of how to prevent H2A.Z.2 from functioning in chromatin.” Chromatin is a mass of genetic material that packages DNA and proteins to fit inside the cell nucleus.
An emerging theory in cancer research is that abnormal cell growth may result not only from mutations in patients’ genes, but also from epigenetic mechanisms, a complex level of gene regulation. Dr. Bernstein’s focus on epigenetics examines histone proteins that package DNA and the factors that influence them as they switch genes on and off.
“There’s a whole world out there that is unknown with regard to the complexity of how normal cells transform and how DNA is packaged and regulated,” says Dr. Bernstein. Her research team found that patients who had higher levels of H2A.Z.2 had worse prognoses than those who did not.
The most promising discovery was that removing H2A.Z.2 from melanoma cells made them more sensitive to chemotherapy and the targeted therapies that focus on genetic mutations. In theory, the new finding could lead to clinical trials that would combine the use of chemotherapy or targeted therapies with a method of depleting a patient’s levels of H2A.Z.2.
Researchers from New York University Langone Medical Center, Ludwig-Maximilians University in Germany, and the Max-Planck Institute of Biochemistry in Germany also collaborated on the study.