Publication Date
7-1-2024
Journal
The EMBO Journal
DOI
10.1038/s44318-024-00099-0
PMID
38773319
PMCID
PMC11217308
PubMedCentral® Posted Date
5-21-2024
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Humans, Animals, Neoplasms, Cell Differentiation, Tumor Suppressor Protein p53, Cell Transformation, Neoplastic, Stem Cells, Carcinogenesis, Differentiation, Multicellularity, p53, Plasticity, Stem Cell, Cancer, Development, Evolution & Ecology
Abstract
A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain the capacity to return to the cell cycle and required the tumor suppressor p53. Finally, we examine an example of an evolutionarily conserved program for the plasticity of differentiated cells, paligenosis, which helps explain the origins of cancers that arise in adults. Altogether, we highlight new perspectives for understanding the development of cancer and new strategies for preventing carcinogenic cellular transformations from occurring.
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Digestive System Diseases Commons, Gastroenterology Commons, Medical Sciences Commons, Oncology Commons