A newly identified protein, ZNF432, may offer a promising target for treating endometrial cancer by slowing tumor growth and triggering cancer cell death, according to a study published recently in Discover Oncology.
In both laboratory and animal studies, increasing levels of ZNF432 in cancer cells significantly reduced tumor progression and enhanced apoptosis, the body’s natural process of eliminating damaged cells.
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Endometrial cancer, which begins in the lining of the uterus, is one of the most common gynecologic cancers worldwide. This study found that ZNF432 was usually underexpressed in cancer tissues compared to healthy tissues, with lower levels seen as tumors became more advanced. Scientists also discovered that a particular cell line, called Ishikawa, had the lowest levels of ZNF432 and was used for further investigation.
“This study highlights the significant underexpression of ZNF432 in endometrial cancer tissues, demonstrating its role as a tumor suppressor by promoting apoptosis and inhibiting cancer cell proliferation,” explained the authors of this study. They continued, “Mechanistically, ZNF432 enhances apoptosis through the ubiquitination of UPF1, providing insights into its potential as a therapeutic target in endometrial cancer treatment.”
When researchers increased ZNF432 in these cells, cancer growth slowed, and more cells underwent apoptosis. By contrast, when ZNF432 was reduced, tumors grew faster and resisted cell death. Mice implanted with cancer cells overexpressing ZNF432 developed much smaller tumors than mice with normal levels of the protein. Tissue analysis confirmed that tumors with high ZNF432 had fewer markers of cell growth and more indicators of apoptosis.
The team uncovered how ZNF432 might work by focusing on its relationship with another protein called UPF1. ZNF432 appeared to interact with UPF1, leading to its breakdown through a natural cell process called ubiquitination. When levels of UPF1 dropped, cancer cells lost their survival signals and became more prone to dying. In experiments where UPF1 was boosted, it reversed many of the tumor-suppressing effects of ZNF432, confirming the connection between these two proteins.
This discovery not only sheds light on how ZNF432 functions but also opens the door for new therapies. If drugs can be developed to raise levels of ZNF432 or mimic its effects, it may provide a more targeted way to treat endometrial cancer.
