View Program - 63rd Annual Drosophila Research Conference

Non-canonical variations of the cell cycle are important in development and disease. One of these variations is the endocycle, which results in large, polyploid cells that arise through inhibition of mitosis. In addition to these developmental endocycling cells (devECs), conditional signals can result in induced endocycling cells (iECs), such as during wound healing, aging, or cancer. We have previously shown in Drosophila that devECs and iECs repress the apoptotic response to DNA damage. With the Walczak lab, we have also shown that transient iECs in both flies and humans can undergo error-prone mitosis (RTM). These data are consistent with mounting evidence that cancer cells can transiently enter the endocycle in response to genotoxic therapies, and can then switch back to error-prone, polyploid mitoses that contribute to genome instability and tumor regrowth. Much remains unknown, however, about how the growth of transient iECs is regulated and how iECs affect tissue homeostasis and tumorigenesis.
We will report our progress using Drosophila as an in vivo model system to decipher how endocycles contribute to normal and abnormal tissue growth. Particularly, we will discuss our investigations into the possible synergies between pro-growth mutations and different variant cell cycles. Although iECs repress apoptosis, we will present evidence that a subset may senesce, depending on developmental context. This work will lead to a greater understanding of growth, proliferation, and checkpoint regulation in polyploid cells, and their effects on tissue homeostasis and cancer.

Regulation of induced endocycling cells and their effects on tissue growth