How gene mutation boosts cancer risk

Date:
November 10, 2021
Source:
University of Virginia Health System
Summary:
Scientists have revealed why a mutation in the UTX gene disrupts
cells' ability to suppress tumors.



FULL STORY ========================================================================== Researchers at the University of Virginia School of Medicine have
discovered how a common gene mutation robs people of natural cancer
protection.


==========================================================================
Hao Jiang, PhD, of UVA Cancer Center, and his collaborators have revealed
why a mutation in the UTX gene disrupts cells' ability to suppress
tumors. The gene product, they found, forms tiny droplets in cells that
help prevent tumor formation. But the mutation throws a wrench in that important process, leaving affected people vulnerable.

The new understanding of this vulnerability will help scientists and
doctors as they seek better ways to battle and prevent cancer.

"How UTX inactivation causes human cancers remained elusive, as we did not
know its key molecular activity that is critical for tumor suppression,
posing a barrier to cancer therapies targeting UTX-related pathways," said Jiang, of UVA's Department of Biochemistry and Molecular Genetics. "Our
work largely solved this mystery. Moreover, it suggests that disruption or alterations of these droplets can profoundly affect how our cells fight
cancer. Forming proper droplets is likely to be a fundamental mechanism
that maintains cellular health, and we are just beginning to understand." Preventing Cancer Tumors Jiang's work gives us a fascinating glimpse
into an important way our bodies keep us safe from cancer. The UTX gene,
he found, plays a vital role by directing the formation of "condensates"
inside cells to prevent tumor formation. These little droplets condense
from material in cells sort of like how water droplets condense on
the outside of a cold glass. Once the droplets have formed, important biological processes can take place.

The droplets are important not just for suppressing tumors, Jiang and
his team found, but for directing embryonic stem cells, generalized
cells that can turn into highly specialized cells. For example, a stem
cell might turn into a nerve cell or become bone.

For tumor suppression, the researchers found, the droplets control
the activity of chromatin, the genetic material contained in our
chromosomes. This ensures chromatin's "optimal activity," the scientists
write in a new paper in the scientific journal Nature. The interaction,
they note, "ensures efficient and correct chromatin modifications and interactions to orchestrate a proper tumour-suppressive transcriptional program." Mutation of the UTX gene, however, robs cells of this
important ability, putting people with the mutation at risk for cancer,
the researchers conclude.

Another interesting finding in this work is that UTY, the Y-chromosome counterpart of UTX in men, forms condensates with more solid-like
properties, making it less effective in suppressing cancer. This may
contribute to the widely observed phenomenon that men are more likely
to get cancer than women.

"We are very interested in how the condensate properties of UTX
are regulated in cells and how other proteins may control cancer
through forming droplets," Jiang said. "These studies will likely open
up new approaches to cancer treatment by regulating these droplets." ========================================================================== Story Source: Materials provided by
University_of_Virginia_Health_System. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Bi Shi, Wei Li, Yansu Song, Zhenjia Wang, Rui Ju, Aleksandra
Ulman, Jing
Hu, Francesco Palomba, Yanfang Zhao, John Philip Le, William
Jarrard, David Dimoff, Michelle A. Digman, Enrico Gratton, Chongzhi
Zang, Hao Jiang. UTX condensation underlies its tumour-suppressive
activity.

Nature, 2021; 597 (7878): 726 DOI: 10.1038/s41586-021-03903-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211110104558.htm

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