Scientists at NYU Abu Dhabi say they have discovered that a single cancer-causing gene can trigger different responses in cells, with some helping to prevent tumors while others may contribute to their development.
The study “UHRF1 overexpression generates senescent states with different T53 dependencies,” published in EMBO Reports, found that the gene can trigger several forms of cellular senescence, a natural defense in which damaged cells stop dividing to help prevent cancer, a tumor-suppressive function inherent to all cells.
Using a zebrafish model of liver cancer, the researchers investigated the initial response to a cancer-causing gene and found that some of these precancerous cells are terminally senescent, meaning they cannot generate tumors, while others can regain the ability to divide and potentially contribute to cancer.
Commonly used chemotherapies frequently cause cancer cells to enter senescence, but do not fully eliminate these cells. Therefore, it is useful to target these therapy-induced senescent cells with senolytics that eliminate them, say the researchers.
In this study, the team tested a common senolytic to investigate its ability to target senescent cells and found that it was effective against only some of the precancerous cells but not others. The findings suggest that treatments targeting senescent cells may need to account for the different ways these cells behave.
“Cancer is not simply a matter of whether a cell stops dividing or continues to grow. Our study shows that there are different types of cellular senescence, and depending on the type acquired by a pre-cancerous cell, the outcome can make the difference between turning into a cancer cell or not,” explained Professor of Biology at NYU Abu Dhabi and senior author Kirsten Sadler Edepli, PhD.
“We also show that these different forms of senescent cells have hugely different responses to treatments, which is important when developing and applying cancer therapies. It is particularly exciting that our undergraduate capstone researchers contributed to this discovery. Their work demonstrates the valuable role students can play in high-impact research when they are given the opportunity to engage directly with important scientific questions and are given dedicated mentors to guide their efforts.”
The research was conducted by NYU Abu Dhabi researchers in collaboration with the University’s Center for Genomics and Systems Biology. The findings provide new insight into how cells respond when cancer-causing genes are activated and could help researchers better understand how different types of senescent cells should be targeted in cancer treatment, according to the investigators.
