Embryogenesis, morphogens and cancer stem cells: putting the puzzle together

Abstract

This paper describes a model which puts together three key elements of cancer theory: the analogies between embryogenesis and carcinogenesis, the role played in both processes by morphogens and related pathways, and the recently emerged paradigm of cancer stem cells. The model is called Epigenetic Tracking. Originally conceived as a model of embryonic development, it was later extended to interpret other aspects of biology, such as the presence of junk DNA, the phenomenon of ageing and the process of cancer formation. In this work we deepen our vision of carcinogenesis, and propose a novel hypothesis on the role of morphogen-processing pathways. According to the hypothesis, the interplay of these pathways leads in stem cells to the production of new transcription factors, which act as drivers of cellular differentiation. The disruption of these pathways, caused by mutations in specific genes, would represent the first and most distinctive event in the carcinogenic process. Our hypothesis allows us to make testable predictions on patterns of gene mutations involved in carcinogenesis. Our hypothesis also suggests that cancer stem cells can stay dormant until they are activated in a process that resembles activation of stem cells during tissue repair or at a specific time during development.