Is Co-option a Prevailing Mechanism during Cancer Progression?

Cancer progression results from the accumulation of genetic and epigenetic alterations that provide tumor cells with a selective advantage. The consecutive cycles of mutations, selections, and clonal expansions generate, over time, descendant cells with increasing malignant properties. Although this conception of tumor develop- ment rests on solid experimental foundations, it has also raised several persisting questions. Does the succession of mutations dictate the progression of each cancer type or does the disturbance of an invariant set of regulatory circuits govern tumor evolution regardless of the linear order of genetic events? Is the ability of malignant cells to disseminate and spawn metastasis a property acquired at late stages of tumor development or is the proclivity to metastasize implanted early during cancer formation? Considering these issues, we elaborate here on the concept of co-option that refers to the emergence of novel functions from ancestral characters during episodes of organismal evolution. As discussed in this Perspective, co-option seems to be a key mechanism propelling the molecular engine that drives malignant transformation. Hence, this notion may constitute a unifying principle that connects a large body of experimental results to clinical observations.