Lessons we can learn from neurons to make cancer cells quiescent.

Abstract

Cancer is a major concern for contemporary societies. However, the incidence of cancer is unevenly distributed among tissues and cell types. In particular, the evidence indicates that neurons are absolutely resistant to cancer and this is commonly explained on the basis of the known postmitotic state of neurons. The dominant paradigm on cancer understands this problem as a disease caused by mutations in cellular genes that result in unrestrained cell proliferation and eventually in tissue invasion and metastasis. However, the evidence also shows that mutations and gross chromosomal anomalies are common in functional neurons that nevertheless do not become neoplastic. This fact suggests that in the real nonexperimental setting mutations per se are not enough for inducing carcinogenesis but also that the postmitotic state of neurons is not genetically controlled or determined, otherwise there should be reports of spontaneously transformed neurons. Here we discuss the evidence that the postmitotic state of neurons has a structural basis on the high stability of their nuclear higher order structure that performs like an absolute tumor suppressor. We also discuss evidence that it is possible to induce a similar structural postmitotic state in nonneural cell types as a practical strategy for stopping or reducing the progression of cancer.