Scientists gain new insights into molecular mechanisms of breast cancer development

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.

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.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Immunotherapy timing key to survival in small cell lung cancer treatment