National Cancer Institute 1ZIABC011832-08

Study cell cycle regulation in dormant tumor cells

This NIH grant supports research on molecular mechanisms regulating cell cycle exit in dormant tumor cells, aiming to develop therapies to halt cancer cell proliferation.

Description

Cells can exit the cell cycle into a number of different states. Temporary cell cycle exit is referred to as quiescence, while more permanent, irreversible cell cycle exit is referred to as senescence. How and why cells choose between these different types of cell cycle exit is not completely known. Understanding the molecular mechanisms that determine whether cells temporarily or permanently exit the cell cycle is of immense interest, because we could develop new therapies to force cancer cells to irreversibly exit the cell cycle, halting tumor growth. To investigate the molecular mechanisms underlying cell cycle exit, we will leverage our platform of long-term single-cell tracking combined with biosensors of key enzyme activities. Using this cutting edge approach, we have previously discovered mechanisms that explain how cells irreversibly exit the cell cycle during senescence through the degradation of MYC. Furthermore, we have investigated molecular mechanisms underlying how quiescent cells are able to re-enter the cell cycle and begin proliferating again, through the dynamic regulation of the anaphase-promoting complex/cyclosome. In the future, this project will continue to investigate mechanisms of cell cycle exit with the goal to develop new therapies to halt uncontrolled cancer cell proliferation.

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