Breast cancers: Ruptures in cell nuclei promotes tumor invasion

Date:
September 23, 2021
Source:
CNRS
Summary:
When cells multiply and migrate, they can be compressed
and their nucleus may break open. This phenomenon causes DNA
damage. Scientists have now shown that this facilitates the spread
of cancer cells in breast tumors.



FULL STORY ==========================================================================
The nucleus of a cell fills a crucial function: to protect cell DNA
and enable its proper use. But it can be deformed, or even temporarily fractured, if the cell itself is compressed and deformed, for example,
in the case of migration or proliferation. This compression then leads to
DNA damage. The consequences are accelerated ageing for healthy cells and
the acquisition of invasive properties for breast tumour cells, as has
just been shown by a research team from CNRS, Institut Curie and INSERM1.


========================================================================== These scientists have shown that when cells are compressed and that
breaks the nucleus, DNA can come into contact with a DNA-destroying
enzyme called TREX1.

TREX1's normal function is to protect the cell by destroying the DNA
of viruses that try to infect it, but under these unusual conditions it
attacks the cell DNA.

In healthy tissue, the cells then show signs of ageing and stop dividing.

However, the research team has observed that the consequences are
different in a breast tumour: instead of killing the cancer cells,
the damage caused by TREX1 will make them more invasive. For example,
when the tumour grows too much, the cells are compressed and then acquire
the ability to destroy their environment to invade neighbouring tissues,
with increased risk of metastasis.

These results reveal the importance of the enzyme TREX1 in the development
of breast cancer and also in ageing. The scientists now want to identify
and test molecules that could block its activity. Because TREX1 has an important role in modulating inflammation and immunity, these inhibitors
may have many applications in therapy.

Notes 1- In France, researchers from the Laboratoire Biologie
Cellulaire et Cancer (CNRS/Institut Curie/Sorbonne Universite'), the Laboratoire Immunite' et Cancer (INSERM/Institut Curie), the Laboratoire Physico-chimie Curie (CNRS/Sorbonne Universite'/Institut Curie), the Laboratoire Processus d'Activation Se'lectif par Transfert d'Energie Uni-e'lectronique ou Radiatif (CNRS/ENS -- PSL/Sorbonne Universite')
and the Centre de Recherche des Cordeliers (INSERM/Universite' de Paris/Sorbonne Universite') participated in this work.

========================================================================== Story Source: Materials provided by CNRS. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Guilherme Pedreira de Freitas Nader, Sonia Agu"era-Gonzalez, Fiona
Routet, Matthieu Gratia, Mathieu Maurin, Valeria Cancila, Clotilde
Cadart, Andrea Palamidessi, Rodrigo Nalio Ramos, Mabel San Roman,
Matteo Gentili, Ayako Yamada, Alice Williart, Catalina Lodillinsky,
Emilie Lagoutte, Catherine Villard, Jean-Louis Viovy, Claudio
Tripodo, Je'ro^me Galon, Giorgio Scita, Nicolas Manel, Philippe
Chavrier, Matthieu Piel.

Compromised nuclear envelope integrity drives TREX1-dependent
DNA damage and tumor cell invasion. Cell, 2021; DOI:
10.1016/j.cell.2021.08.035 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210923115630.htm

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