Reactive oxygen species (ROS) from mitochondria are key drivers of genetic chaos in cancer by causing the collapse of micronuclear envelopes, a process that fuels the chromosomal instability (CIN) often observed in aggressive tumor behavior. These are the findings of two new studies. The findings identify key proteins in this destructive process – p62 and CHMP7 – revealing potential prognostic markers and therapeutic targets for high-CIN tumors.
Errors in chromosome segregation during cell division can lead to chromosomal instability, a key feature of cancer. These errors result in the formation of micronuclei, which are small structures separate from the main nucleus that often contain lagging chromosomes or fragments. Unlike the main nucleus, micronuclei frequently rupture, releasing their DNA into the cytoplasm of the cell.
This release causes DNA damage and genomic instability. It activates an immune response that can drive tumor-related inflammation and metastasis that can promote cancer progression. However, the mechanisms and molecular underpinnings governing micronuclear collapse are poorly understood.
Across two studies, researchers reveal the mechanisms that compromise micronuclear envelope integrity and disrupt the normal activity of the cellular machinery responsible for nuclear membrane repair (i.e., ESCRT-III complex).
They show how both mechanisms are triggered by ROS and contribute to micronuclear collapse. Using proteomic analysis and genetic manipulation.