A new mechanism has been discovered that can make breast cancer metastatic. At the center there is a variant of the p63 protein whose presence is in turn closely linked to the characteristics of the tumor microenvironment.
To make a tumor dangerous is usually its ability to form metastases, that is to invade tissues and organs far from their place of origin. This is why it is important to understand the molecular mechanisms that guide its diffusion in the organism. In the case of breast cancer, one more step in this direction was made by the research group of Prof Matilde Todaro of the University of Palermo. Thanks to a study conducted with the irreplaceable funding of AIRC, Todaro and colleagues have described the fundamental role of a particular variant of p63 protein in making malignant cells, and therefore able to metastasize, breast cancer cells.
“It all started with the observation that different variants of the p63 protein (and relative RNA) are expressed in metastatic and non-metastatic tumor cells”, explains the researcher. “More precisely, we realized that metastatic tumor cells had a greater abundance than a particular variant of p63 called DeltaNp63. Conversely, the cells in which another variant was more abundant – TAp63 – were less invasive “.
The next step was to try to understand the reasons for the abundance of DeltaNp63 in the most malignant cells. The experiments conducted, described in the pages of Oncotarget, show that the game is the tumor microenvironment, e.g. the set of cells and substances in which the tumor is immersed. It is precisely the particular molecules present in this environment that drive the higher expression of DeltaNp63 to the detriment of TAp63.
The researchers also found that DeltaNp63 increases the expression of PI3K and CD44v6, two molecules already known for their involvement in the proliferative and metastatic capacity of colon cancer cells. DeltaNp63 is therefore upstream of a molecular cascade that increases tumor malignancy. “In practice – Todaro makes clear – this molecule does nothing but activate a very convenient path for the tumor itself”. The good news is that there are already inhibitors of these molecules and Todaro and colleagues have shown their effectiveness, in isolated cells and with laboratory animals, in blocking the proliferation and spreading capacity of tumor cells with DeltaNp63 variant. An observation that opens up to the possible development of new therapeutic strategies.