Study identifies new protection mechanism in breast cancer

Date:
March 22, 2022
Source:
Karolinska Institutet
Summary:
Researchers have identified a protein that protects against breast
tumor growth and that can be linked to a better prognosis in breast
cancer patients. The results may contribute to the development of
new therapies for difficult-to-treat forms of breast cancer.



FULL STORY ========================================================================== Researchers at Karolinska Institutet in Sweden have identified a protein
that protects against breast tumour growth and that can be linked to
a better prognosis in breast cancer patients. The results, which are
published in the journal Nature Communications, may contribute to the development of new therapies for difficult-to-treat forms of breast
cancer.


========================================================================== Breast cancer affects about 10 per cent of women during their lifetime
and is a major medical and societal burden. Fewer treatment options are available for ER-negative breast cancers, which lack oestrogen receptors
(ER) and thus do not respond to hormone therapy. Particularly difficult
to treat are so-called triple-negative breast cancers, which lack not
only ER but also the progesterone receptor and HER2 receptor.

"Identification of new molecular mechanisms that regulate the growth
of ER- negative breast cancer is warranted, as these mechanisms may
represent novel therapeutic targets," says Per Uhle'n, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.

Professor Uhle'n and colleagues have identified a novel mechanism by
which the ubiquitous protein GIT1 regulates so-called Notch signalling, affecting the initiation and growth of ER-negative breast cancer.

Associated with better prognosis Studies of tumour cells from breast
cancer patients showed that high levels of GIT1 inhibited Notch signalling
and protected against tumour growth, while low levels of GIT1 enhanced
tumour growth. ER-negative breast tumours from patients had lower levels
of GIT1 than ER-positive breast tumours. The results also showed that ER-negative breast cancer patients with high levels of GIT1 have a better prognosis than those with low levels.

Notch signalling is an evolutionarily conserved cell-cell
communication mechanism that has been shown to regulate cell fate
decisions in most organs of the body and at different steps during cell development. Overactive Notch signalling in breast cancer patients has previously been linked to a worse prognosis.

"Our results provide important information about a mechanism that controls
the initiation and growth of breast tumours," says Professor Uhle'n. "We
hope that these findings will inform the development of new therapies
for patients with difficult-to-treat breast cancer." Collaboration with
the clinic His research group is actively collaborating with clinicians treating patients with cancer to focus on research topics that are
crucial for the treatment of patients.

"We want to conduct research that can benefit patients with severe
diseases," says Professor Uhle'n. "At Karolinska Institutet, we have state-of-the-art tools and equipment that can push the development of new therapies." The research was carried out at Karolinska Institutet with
funding from, among others, the Swedish Research Council, the Swedish
Cancer Society and the Wallenberg Academy Fellow grant from the Knut
and Alice Wallenberg Foundation.

The authors declare no competing interests.


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


========================================================================== Journal Reference:
1. Songbai Zhang, Ayako Miyakawa, Malin Wickstro"m, Cecilia Dyberg,
Lauri
Louhivuori, Manuel Varas-Godoy, Kati Kemppainen, Shigeaki Kanatani,
Dagmara Kaczynska, Ivar Dehnisch Ellstro"m, Lotta Elfman, Pauliina
Kronqvist, Heli Repo, Katsuhiko Mikoshiba, Cecilia Sahlgren, John
Inge Johnsen, Per Uhle'n. GIT1 protects against breast cancer growth
through negative regulation of Notch. Nature Communications, 2022;
13 (1) DOI: 10.1038/s41467-022-28631-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220322111253.htm

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