Scientists at IRB Barcelona’s Development and Growth Control Laboratory have made a significant discovery on how DNA damage caused by chromosomal instability (CIN) can increase the invasiveness of cancer cells. This research, led by ICREA researcher Marco Milán, PhD, provides valuable insights into the metastatic process, which is responsible for 90% of cancer-related deaths. The findings were published in Current Biology.
Chromosomal instability is a common characteristic of human cancers and is associated with the mutation of CIN genes. This mutation increases the likelihood of gaining or losing whole chromosomes or large portions of them during cell division. The study reveals that this instability activates the JAK/STAT signaling pathway and promotes caspase activity, resulting in DNA damage. This damage enables cancer cells to escape from the primary tumor and metastasize.
By using a Drosophila epithelial model, the researchers demonstrated that DNA damage occurs as a result of lagging chromosomes during mitosis and replicative stress induced by aneuploidy. They also discovered a pro-invasive role of caspases in enhancing CIN-induced DNA damage. Furthermore, they identified the JAK/STAT signaling pathway as an activator of apoptotic caspases by inducing the expression of pro-apoptotic genes.
Traditionally, caspases were believed to induce cell death in response to DNA damage. However, this study reveals that they may also play a role in promoting DNA damage and invasiveness. Understanding this new aspect of cancer biology opens doors to exploring novel therapeutic approaches to target metastasis.
This research builds upon the laboratory’s previous studies on chromosomal instability and its effects on cancer and metastasis. In this work, the scientists investigate the role of DNA damage as the third axis of action in stimulating cancer cell invasiveness. They reveal that aneuploidy stimulates the JAK/STAT pathway, leading to caspase activation and subsequent DNA damage.
This groundbreaking study provides valuable knowledge on the mechanisms behind cancer cell invasiveness and metastasis. It sheds light on the complex interplay between chromosomal instability, DNA damage, and cellular processes that drive cancer progression. With further research, this understanding could pave the way for the development of targeted therapies to combat metastatic cancer.