Whole-Genome Doubling as a source of cancer: how, when, where, and why?

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Javier De Las Rivas¹  Guillermo de Cárcer²  Natalia Sanz-Gómez²  María González-Álvarez² 

[1] Bioinformatics and Functional Genomics Group, Cancer Research Center (CiC-IBMCC), Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca (USAL), Salamanca, Spain;Cell Cycle and Cancer Biomarkers Laboratory, Cancer Biology Department, Instituto de Investigaciones Biomédicas “Alberto Sols“. (IIBM) CSIC-UAM, Madrid, Spain;

关键词: whole-genome doubling;    oncogene;    aneuploidy;    polyploidy;    chromosomal instability;    endoreduplication;    mitotic slippage;   

DOI  :  10.3389/fcell.2023.1209136

 received in 2023-04-20, accepted in 2023-05-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

Chromosome instability is a well-known hallmark of cancer, leading to increased genetic plasticity of tumoral cells, which favors cancer aggressiveness, and poor prognosis. One of the main sources of chromosomal instability are events that lead to a Whole-Genome Duplication (WGD) and the subsequently generated cell polyploidy. In recent years, several studies showed that WGD occurs at the early stages of cell transformation, which allows cells to later become aneuploid, thus leading to cancer progression. On the other hand, other studies convey that polyploidy plays a tumor suppressor role, by inducing cell cycle arrest, cell senescence, apoptosis, and even prompting cell differentiation, depending on the tissue cell type. There is still a gap in understanding how cells that underwent WGD can overcome the deleterious effect on cell fitness and evolve to become tumoral. Some laboratories in the chromosomal instability field recently explored this paradox, finding biomarkers that modulate polyploid cells to become oncogenic. This review brings a historical view of how WGD and polyploidy impact cell fitness and cancer progression, and bring together the last studies that describe the genes helping cells to adapt to polyploidy.

【 授权许可】

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Copyright © 2023 Sanz-Gómez, González-Álvarez, De Las Rivas and de Cárcer.