Trends in Cell Biology
ReviewEndoreplication: The Good, the Bad, and the Ugly
Section snippets
Endoreplication, an Alternative Cell Cycle Program
The cell cycle is spatiotemporally regulated in multicellular organisms, the precision of which ensures that the daughter cells maintain the same amount of genetic content as the mother cell. The most common cell cycle progression is the G1-S-G2-M cycle, or the ‘mitotic cycle’ (Figure 1A). The mother cell prepares itself during the G1 and G2 phases, replicates its DNA during the DNA synthesis (S) phase, and splits the DNA equally between two daughter cells during the mitosis (M) phase. By
Development
Polyploid cells are essential for achieving normal size and functionality of a range of tissues and organs [4]. Endoreplication-induced polyploidy plays a pivotal role in tissue development in various organisms, and is usually an irreversible process that is responsible for terminal cell differentiation. In mammals, endoreplication and polyploidy are observed in multiple tissues and organs during normal development, including the skin, placenta, liver, and blood [4]. In placenta, trophoblast
Cancer: An Ugly Consequence of Endoreplication and Polyploidization
Although endoreplication and polyploidization play positive and sometimes essential roles in many developmental and homeostatic processes, they have been implicated in primary tumor formation, cancer progression and metastasis, and cancer relapse (Figure 3). Clinically, endoreplication and polyploidy have been observed in cancer tissues [55], with their occurrence ranging from 11% in stomach carcinoma to 54% in liver adenocarcinomai. Although it is not clear how endoreplicating cells overcome
Concluding Remarks
Endoreplication is widespread in animals and plants. It plays critical roles in the development of organisms, and is tightly regulated by intrinsic mechanisms that are unique to the context. It also has been regarded as a key mechanism to repair tissue damage and maintain homeostasis. Recent advances in these areas suggest that mechanical forces and related signaling pathways are linkers between polyploidization and tissue homeostasis; however, a mechanistic understanding of the entire process
Acknowledgments
We thank Sarah Ogden and Allison Jevitt for providing assistance in figure preparation, Yoichiro Tamori and Sheng-An Yang for inputs, and Jen Kennedy for proofreading the manuscript. This work was supported by grants from National Science FoundationIOS-1052333 and National Institutes of HealthR01GM072562 to W-M.D.
Glossary
- Compensatory cellular hypertrophy (CCH)
- a tissue homeostasis mechanism through which postmitotic cells undergo hypertrophic growth to compensate for the lost tissue volume.
- Endoreplication
- the replication of DNA during the S phase of the cell cycle without the subsequent completion of mitosis and/or cytokinesis.
- Endomitosis
- the genome is replicated and mitosis is initiated but not completed, resulting in mononucleated or binucleated polyploid cell.
- Polyploid cells
- cells containing more than two sets
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