Source: Weizmann Institute of Science
Summary: When cancer’s attack is underway, it may even cause a gene that acts as the body’s master defender to change allegiance. A study that was reported recently has discovered that the betrayal of this gene can occur in more ways than previously appreciated.
All cells carry this gene, known as p53. This gene normally plays a central role in protecting the body against malignancy, orchestrating the cell’s defenses against cancer and often killing a potentially cancerous cell if these fail. In about half of cancer patients, the p53 gene within the cancerous cells contains alterations – mutations – that can result in the production of a p53 protein that not only fails to suppress cancer but can even launch cancer-promoting activities. In the initial stages of cancer development, the microenvironment is hostile to the tumor. When cancer’s attack is underway, it may even cause a gene that acts as the body’s master defender to change allegiance. A study that was reported recently by the researchers of Weizmann Institute of Science has discovered that the betrayal of this gene can occur in more ways than previously appreciated. The study findings were published in the journal Proceedings of the National Academy of Sciences.
In the study, the researchers showed that eliminating the p53 protein from cancer-associated fibroblasts by silencing their p53 genes caused these cells to lose many of their tumor-supporting features and behave more like normal fibroblasts. In particular, the silencing of fibroblast p53 reduced the migration of adjacent cancer cells in a laboratory dish, a crucial change, considering that invasive migration facilitates the metastatic spread of cancer. Moreover, the silencing of p53 in cancer-associated fibroblasts greatly reduced the ability of these cells to promote tumor growth in mice. Finding ways to “re-educate” the renegade p53 in the tumor microenvironment – to reverse its behavior back to suppressing tumors – may pave the way to the development of novel therapies that will target the microenvironment rather than the cancer cells themselves. Indeed, strategies targeting the cancer microenvironment are being increasingly explored in recent years.
The hope is that they might provide a new window of opportunity for launching effective therapy because the microenvironment tends to evolve more slowly than the mutation-ridden tumor cells.
More Information: Sharathchandra Arandkar et al, “Altered p53 functionality in cancer-associated fibroblasts contributes to their cancer-supporting features, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1719076115