My watch list
my.bionity.com  
Login  

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

11-Jan-2017

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.

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.

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.

Facts, background information, dossiers
More about Universität Basel
  • News

    Why Some Forms of Leukemia Only Affect Children

    Acute myeloid leukemia (AML) mainly affects children, with the prognosis often being poor despite several decades of research into more effective treatments. A new study led by researchers from the University of Basel and from Gustave Roussy Institute, Paris, explains why some forms of leuk ... more

    A new strategy for the synthesis of complex natural products

    Chemists from the University of Basel have succeeded in synthesizing two complex natural products from the group of dithiodiketopiperazines (DTPs). For this, they employed a new strategy based on “C-H bond activation,” resulting in a short and high yielding route. In the of the Journal of t ... more

    Too much of a good thing: overactive immune cells trigger inflammation

    Scientists describe a previously unknown disorder of the immune system: in a distinct subset of immune cells from patients with primary immunodeficiency, cellular respiration is significantly increased. This cellular metabolic overactivity leads to inflammation, as an international research ... more

  • Videos

    Virtual Reality in Medicine: New Opportunities for Diagnostics and Surgical Planning

    Before an operation, surgeons have to obtain the most precise image possible of the anatomical structures of the part of the body undergoing surgery. University of Basel researchers have now developed a technology that uses computed tomography data to generate a three-dimensional image in r ... more

    Nuclear Pores Captured on Film

    Zooming into a nuclear pore complex using a high-speed atomic force microscope reveals the selectivity barrier that filters the traffic of molecules passing between the cytoplasm and nucleus in eukaryotic cells. This is comprised of intrinsically disordered proteins known as FG Nucleoporins ... more

Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE