João Pedro de Magalhães proposed that cancer protection may limit regeneration
João Pedro de Magalhães proposed that cancer protection may limit regeneration
On August 27, he proposed that developmental transitions may have limited tissue repair to reduce cancer risk.
On August 22, Michael West asked whether a brief reprogramming signal would be enough to repair a large area of damaged tissue. De Magalhães added a safety condition to this question: restoring regenerative capacity may weaken tumor suppression.
Partial reprogramming temporarily returns an adult cell to a younger pattern of gene activity while preserving its specialized identity. Repairing damaged tissue requires cells to divide and build a new structure. This growth must also remain controlled because uncontrolled cell division produces a tumor.
In a post referring to a paper in Nature Reviews Cancer, de Magalhães stated the hypothesis as follows:
“I hypothesize that developmental transitions limit regenerative capacity partly because this reduces cancer risk.”
According to this evolutionary hypothesis, natural selection may have preserved mechanisms that reduced cancer risk in young organisms. The same mechanisms stop dangerous cell division and may constrain regeneration after tissue damage. Two animal experiments demonstrate this conflict in specific biological systems.
In a 2010 study in mice, researchers found no p21, a protein involved in stopping cell division, in connective tissue cells from the ears of MRL mice, a strain that efficiently closes holes in its ears. Ear holes in mice lacking p21 closed in a manner similar to those in MRL mice. In a 2015 study in zebrafish, researchers introduced the human ARF gene, which helps suppress tumor growth, into the genome. After fin amputation, ARF became active in the blastema, a mass of dividing cells from which the fin regrows. In a separate experiment, temporary activation of ARF inhibited regeneration through p53, a system that controls cell division.
Studies of partial reprogramming must test both whether the intervention restores the tissue’s regenerative capacity and whether control of cell division remains intact.