New insights into mechanisms of breast cancer development and resistance to therapy

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We recently published a work on the tumor suppressor LATS as a key player in the development and treatment of breast cancer. See below the press release by the University of Basel.

Uninews release

Why does breast cancer develop and how come certain patients are resistant to established therapies? Researchers from the University of Basel have gained new insights into the molecular processes in breast tissue. They identified the tumor suppressor LATS as a key player in the development and treatment of breast cancer. The journal Nature has published the results today.

All breast cancers are not created equal. In up to 70 percent of all breast cancers, the tumor has receptors for the hormone estrogen. Today, these estrogen-receptor-positive cancers can be treated relatively well. Because these tumors need estrogen for their growth, the receptor is the target of a number of drugs that interfere with estrogen expression, bind to the receptor or speed up its degeneration. However, around a third of all patients does not react to therapy or develops resistance. So far it has not been possible to accurately predict who will respond to this therapy, because the underlying molecular mechanisms are not yet understood entirely.

In a comprehensive molecular study, a group of scientists led by Prof. Mohamed Bentires-Alj from the Department of Biomedicine at the University and the University Hospital of Basel has now identified an important player in this process named LATS. They were able to show how this enzyme, in cooperation with other proteins, influences the development and treatment of breast cancer.

Tumor suppressor LATS decides cell fate
The researchers focused on cancer-inhibiting genes that prevent normal cells from becoming cancerous. In particular, they studied the tumor suppressors LATS1 and LATS2. Once LATS is deleted, the processes in the breast tissue change.

Without LATS, the number of so-called luminal precursor cells in the epithelial tissue of breast glands increases. These are the cells of origin of most types of breast cancer in humans. “LATS balances cell fate in the breast tissue. In its absence the equilibrium shifts and more cells that can give rise to tumors develop”, explains Bentires-Alj.

Related links

Research group Prof. Mohamed Bentires-Alj
Resistance to degradation
In healthy breast tissue, LATS brings together the estrogen receptor alpha with the protein degradation machinery. Without LATS the receptor can no longer be properly degraded, which has consequences for cancer therapy. “We were able to show that cancer cells without LATS no longer respond to Fluvestrant, an estrogen-receptor antagonist that promotes its degradation. They were resistant”, says Bentires-Alj.

The removal of LATS also stabilized the proteins YAP and TAZ, which are upregulated in many cancers and boost cell proliferation. “Thanks to our newly gained insights into the molecular processes in healthy breast tissue, we now also better understand how cells of origin of cancer expand and why certain tumors are resistant to therapy”, summarizes the Basel scientists Bentires-Alj.

Original source

Adrian Britschgi, Stephan Duss, Sungeun Kim, Joana P. Couto, Heike Brinkhaus, Shany Koren, Duvini De Silva, Kirsten D. Mertz, Daniela Kaup, Zsuzsanna Varga, Hans Voshol, Alexandra Vissieres, Cedric Leroy, Tim Roloff, Michael B. Stadler, Christina H. Scheel, Loren J. Miraglia, Anthony P. Orth, Ghislain M. C. Bonamy, Venkateshwar A. Reddy & Mohamed Bentires-Alj
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with Erα Nature (2017), doi: 10.1038/nature20829

Best lightning talk prize for Atul Sethi at the All SystemsX.ch Day 2016

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Around 200 researchers took part in the All SystemsX.ch Day in Bern on September 1st, 2016. Among the participants, Atul Sethi, a post-doctoral associate in Michael Stadler’s lab at the FMI and Momo’s lab at DBM, received the prize for the best lightning talk. He presented the work on studying breast tumor heterogeneity using single cell RNA-sequencing, performed in collaboration with Milan Obradovic, a post-doctoral associate in Momo’s lab at DBM.

Here is the press release of the event.
Michael Stadler’s lab website.

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Image credits/sources: SystemsX.ch
http://www.systemsx.ch/events-education/events/all-systemsxch-day/all-systemsxch-day-2016/
https://myalbum.com/album/v1ln5ui1Asqg

Mohamed Bentires-Alj has been elected to the membership of EMBO

EMBO

 

Mohamed Bentires-Alj of the FMI has been elected to the membership of the European Molecular Biology Organization (EMBO). He is among the 58 outstanding life scientists from Europe and elsewhere newly elected for EMBO.

FMI press release

“I am delighted by the addition of 58 outstanding scientists to our membership […]”, EMBO Director Maria Leptin stated. “By serving the principles of excellence and integrity through their views and actions, they make invaluable contributions to science and society.”

In recent years, Mohamed Bentires-Alj has made significant contributions to advances in his field and to cross-pollination with other fields and communities.

Mohamed Bentires-Alj holds an interest in the mechanisms that regulate normal and neoplastic breast cell heterogeneity: What causes heterogeneity, how therapy influences it and how one can get around it? Working together with his research group he has identified signaling pathways that influence normal and neoplastic breast stem cells, metastasis, and resistance to targeted therapies at the molecular, cellular, and whole organism levels. The Advanced ERC Grant, STEM-BCPC, focuses on signal transduction and epigenetic mechanisms of breast cell plasticity and cancer. This interdisciplinary project seeks to elucidate the integrated effects of signaling pathways and epigenetics on breast cell fate and tumor heterogeneity, and to leverage this mechanistic understanding into therapy. He is developing a personalized medicine program in collaboration with clinicians.

Each year, EMBO elects leading scientists as EMBO Members on the basis of proven excellence in research. With his election, Bentires-Alj figures – along with 13 other FMI scientists – among Europe’s top 1500 life scientists. EMBO Members provide scientific expertise to the fellowship and conference programs coordinated and funded by EMBO, as well as participate in projects to promote the public dissemination of scientific knowledge.

 

 

Bruno Speck Award 2016

Bruno Speck Award 2016
Bruno Speck Award 2016

During the Basel Stem Cell Network Annual Meeting 2016, Shany Koren obtained the Bruno Speck Award for her publication: “PIK3CA-H1047R induces multipotency and multilineage mammary tumors”. Congratulations !

In 2012, Nicola Aceto, PhD student in the lab, also obtained his award for his paper “Tyrosine phosphatase SHP2 promotes breast cancer progression andmaintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.”

Nicola Aceto / Momo / Shany Koren