Endoreplication: The Good, the Bad, and the Ugly

Abstract

To battle adverse internal and external conditions and maintain homeostasis, diploid organisms employ various cellular processes, such as proliferation and apoptosis. In some tissues, an alternative mechanism, endoreplication, is employed toward similar goals. Endoreplication is an evolutionarily conserved cell cycle program during which cells replicate their genomes without division, resulting in polyploid cells. Importantly, endoreplication is reported to be indispensable for normal development and organ formation across various organisms, from fungi to humans. In recent years, more attention has been drawn to delineating its connections to wound healing and tumorigenesis. In this Review, we discuss mechanisms of endoreplication and polyploidization, their essential and positive roles in normal development and tissue homeostasis, and the relationship between polyploidy and cancer.

Keywords: compensatory cellular hypertrophy; development; endoreplication; polyploid giant cancer cells; polyploidy.

Figure 1

Comparison between the mitotic cycle and endocycle A. The mitotic cycle comprises the G1, S, G2, ad M phases. A cell divides into two daughter cells. B. The endocycle only has the G and S phases. Through endoreplication, a cell increases its DNA content without cell division.

Figure 2

Examples of endoreplication in Drosophila A. During development, adult ovarian follicle cells and germline cells become polyploid. B. In Drosophila larva, salivary gland cells are polyploid. C. Polyploid cells are observed in the ileum region of hindgut in the larval Drosophila. D. In post-mitotic tissues like the follicular epithelium, compensatory cellular hypotrophy (CCH) takes place after tissue volume loss.

Figure 3

Endoreplication and cancer A. When treated with antimitotic drugs, diploid cancer cells may undergo cell cycle arrest and cell death, leading to cancer remission; they may enter endoreplication and become polyploid, fueling cancer progression. B. Polyploid giant cancer cells (PGCC) may generate progeny cells through budding; they may also undergo depolyploidization and return to mitosis, which may result in aneuploid cancer cells.