A Double-Edged Sword: How Oncogenes And Tumor Suppressor Genes Can Contribute To Chromosomal Instability
Cells rely on an intricate network of signaling pathways to govern a number of processes ranging from tissue repair to programmed cell death. De-regulation of signaling pathways is a hallmark of cancer and responsible for driving tumor formation.
Aneuploidy, defined as an abnormal chromosome number, is a distinct feature commonly observed in most solid tumors that arises from errors in cell division during mitosis. While some tumors maintain a stably aneuploid genome, many cancer cells persistently mis-segregate their chromosomes during mitosis, a phenomenon known as chromosomal instability (CIN). CIN is thought to drive the genomic re-shuffling that enables cells to acquire new phenotypes such as drug resistance and is intimately associated with loss of mitotic fidelity.
Emerging data show that CIN and de-regulated cell signaling pathways are closely interrelated suggesting the roles that signaling pathways play in the accuracy of mitosis may be underappreciated. These results imply that the induction of CIN can no longer be thought of as a separate event from the cancer-associated driver mutations found in cell signaling pathways. In the context of tumorigenesis this may turn out to be a double-edged sword that combines de-regulated cell cycle progression with the disruption of mitosis to generate the highly complex genomic rearrangements typical of solid tumors. These results change the way we think about how to intervene therapeutically in cancer patients and provide insights on the molecular targets that may contribute significantly to improve patient prognosis.
A double-edged sword: how oncogenes and tumor suppressor genes can contribute to chromosomal instability, Frontiers in Oncology