Marco Milán
ICREA researcher at IRB Barcelona
The work is a clear example of the Darwinian evolution of cancer cells, in this case, of pancreatic cancer. These cells need the Wnt growth factor in order to grow. The authors show that in the absence of Wnt, cancer cells amplify the Myc oncogene (a target of Wnt and an important gene for tumour growth) in extrachromosomal DNA in order to survive.
However, the presence of tens or hundreds of copies of extrachromosomal DNA has a cost: it induces genomic instability. Therefore, when cancer cells are exposed to Wnt again, the extrachromosomal DNA copies are reduced, as Myc is not necessary for their survival. It is a spectacular example of the capacity of tumour cells to modulate the levels of expression of an oncogene using a very novel mechanism (extrachromosomal DNA) only when necessary (given that it has a negative cost) and in the face of external stress (absence of a growth factor).