Mount Sinai Study Provides New Information on Cancer Cellular Pathways

Mount Sinai researchers have pioneered the understanding of the MDM2 gene – which is often overexpressed in cancer – by discovering that, when it acts with a specific protein, it can lead to cancer cell death. The study appears in the print edition of May 2, 2019 Molecular cell.

Their findings provide new insights into cancer-causing cell pathways and could open new therapeutic opportunities for cancer treatment.

Cancer cells are known to modify the methods by which they consume and produce energy. The exact role and function of MDM2, whose chronic expression is seen in cancer, was previously unknown to scientists. This is partly explained by the fact that MDM2 is characterized by both an oncogene – a mutated gene capable of transforming normal cells into cancer cells – and a tumor suppressor.

By studying human cancer cells, fruit flies and genetically modified mice, researchers have shown that when additional copies of the MDM2 gene appear in cancer, their presence disrupts cellular processes. Specifically, they discovered that MDM2 interacted with a protein found in the mitochondria of cancer cells – the part of a cell that produces its energy, and therefore its life – as part of a process that ends up promote the death of cancer cells.

In addition, the team discovered that nutlin-3A, a promising treatment, enhanced the interaction between MDM2 and mitochondrial protein and thus help kill cancer cells. This research also shows that MDM2 can be targeted in an innovative way to promote its interaction with mitochondrial protein in cancer cells to encourage their death.

"Future research should focus on the biology of MDM2 and its pharmacological regulation, as well as the examination of cellular respiration and mitochondrial dynamics." Understanding the exact nature of cellular responses to MDM2-induced stress will contribute to Progress in our efforts to develop concrete therapeutic treatments for cancer ", explains the manager. Jerry Chipuk, Researcher, Associate Professor of Oncology Science and Dermatology, and Associate Director of Shared Resources in Basic Sciences at the Tisch Institute Against Cancer.