Newly discovered microRNA regulates mobility of tumor cells

October 27, 2017, University of Basel
Epithelial breast cancer cells following treatment with an EMT activator: they adopt the properties of mesenchymal cells; in addition, individual cells break away from the cell cluster and migrate into the surrounding tissue. Blue: nucleus, green: paxillin (adhesion protein), red: actin (cytoskeleton). Credit: University of Basel, Department of Biomedicine

Cancer cells can reactivate a cellular process that is an essential part of embryonic development. This allows them to leave the primary tumor, penetrate the surrounding tissue and form metastases in peripheral organs. In the journal Nature Communications, researchers from the University of Basel's Department of Biomedicine provide an insight into the molecular networks that regulate this process.

During an embryo's development, epithelial cells can break away from the cell cluster, modify their cell type-specific properties, and migrate into other regions to form the desired structures there. This process, which is known as an epithelial–mesenchymal transition (EMT), is reversible and can also proceed in the direction from to (MET). It is repeated multiple times during and ultimately paves the way for the formation of organs in the human body.

Tumor cells can reactivate the program

Although this is a completely normal process during embryogenesis, it also plays an important role in the spread of within the body and in the formation of metastases. As a result, this cellular program has also attracted greater attention in the field of tumor research in recent years.

Tumor cells are able to reactivate the EMT/MET program. By doing so, they obtain characteristics of stem cells and develop increased resistance to not only classical but also state-of-the-art targeted cancer therapies.

An EMT also makes it easier for to break away from the , to penetrate into surrounding tissue and into blood vessels, to spread throughout the body and to form metastases in distant organs, which is ultimately responsible for the death of most cancer patients.

The research group, led by Professor Gerhard Christofori from the University of Basel's Department of Biomedicine, researches the molecular processes that regulate the cellular EMT program. By doing so, they aim to demonstrate new intervention strategies to combat the development of malignant tumors and the formation of metastases – such as in the case of breast cancer, one of the most common and malicious diseases in women.

Newly discovered microRNA inhibits EMT

In a study published in the latest edition of Nature Communications, the researchers focused specifically on microRNAs (miRNAs), a class of very short non-coding RNAs with a considerable effect on gene regulation. They identified a hitherto unknown microRNA, miR-1199-5p, that induces epithelial cell behavior and impedes the malignancy of tumor cells, as well as their potential to form secondary tumors.

In concrete terms, the newly discovered microRNA prevents the synthesis of a specific protein, the transcription factor Zeb1, which activates EMT/MET – but if it is missing, the EMT process is prevented. Zeb1 also suppresses the expression of miR1199-5p in what is known as a negative feedback loop, whereby the two molecules regulate one another reciprocally.

More and more often, molecular switches of this kind are being found within processes that cause to alter or lose their cell type-specific properties. They appear to be responsible for a rapid, reversible cellular response to extracellular stimuli.

In the future, these insights into the for regulating EMT/MET plasticity may allow the development of new strategies for the treatment of breast cancer.

Explore further: How a non-coding RNA encourages cancer growth and metastasis

More information: Maren Diepenbruck et al. miR-1199-5p and Zeb1 function in a double-negative feedback loop potentially coordinating EMT and tumour metastasis, Nature Communications (2017). DOI: 10.1038/s41467-017-01197-w

Related Stories

How a non-coding RNA encourages cancer growth and metastasis

August 21, 2017
A mechanism that pushes a certain gene to produce a non-coding form of RNA instead of its protein-coding alternative can promote the growth of cancer, report researchers at the Medical University of South Carolina (MUSC) ...

A new T-cell population for cancer immunotherapy

May 23, 2017
Scientists at the University of Basel in Switzerland have, for the first time, described a new T cell population that can recognize and kill tumor cells. The open access journal eLife has published the results.

Cancer metastasis: The unexpected perils of hypoxia

May 11, 2017
The low oxygen concentrations that prevail in many tumors enhance their propensity to metastasize to other tissues. Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich led by Professor Heiko Hermeking have now ...

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

January 9, 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 ...

Why tumor cells leave home

June 11, 2013
(Medical Xpress)—Malignant cells can escape from primary tumors and colonize new sites in other tissues. In a new study, LMU researchers show how the transcription factor AP4 promotes the development of such metastatic ...

Recommended for you

From the ashes of a failed pain drug, a new therapeutic path emerges

November 16, 2018
In 2013, renowned Boston Children's Hospital pain researcher Clifford Woolf, MB, BCh, Ph.D., and chemist Kai Johnsson, Ph.D., his fellow co-founder at Quartet Medicine, believed they held the key to non-narcotic pain relief. ...

Repurposing FDA-approved drugs can help fight back breast cancer

November 16, 2018
Screening Food and Drug Administration (FDA)-approved compounds for their ability to stop cancer growth in the lab led to the finding that the drug flunarizine can slow down the growth of triple-negative breast cancer in ...

Traditional chemotherapy superior to new alternative for oropharyngeal cancers

November 16, 2018
A drug increasingly used in combination with radiotherapy to treat a type of cancer that forms in the tonsils or the base of the tongue is inferior to a previously favored option, according to a large, clinical trial led ...

New 'SLICE' tool can massively expand immune system's cancer-fighting repertoire

November 15, 2018
Immunotherapy can cure some cancers that until fairly recently were considered fatal. In addition to developing drugs that boost the immune system's cancer-fighting abilities, scientists are becoming expert at manipulating ...

Standard chemotherapy treatment for HPV-positive throat cancer remains the most effective, study finds

November 15, 2018
A new study funded by Cancer Research UK and led by the University of Birmingham has found that the standard chemotherapy used to treat a specific type of throat cancer remains the most effective.

Anti-malaria drugs have shown promise in treating cancer, and now researchers know why

November 15, 2018
Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what the chloroquines were targeting when they attack a tumor. Now, researchers from the Abramson ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.