Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Silencing the Speech Gene FOXP2 Causes Breast Cancer Cells to Metastasize

23.10.2014

It is an intricate network of activity that enables breast cancer cells to move from the primary breast tumor and set up new growths in other parts of the body, a process known as metastasis.

Now a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has identified an unexpected link between a transcription factor known to regulate speech and language development and metastatic colonization of breast cancer.

Currently described online in Cell Stem Cell, the new findings demonstrate that, when silenced, the FOXP2 transcription factor, otherwise known as the speech gene, endows breast cancer cells with a number of malignant traits and properties that enable them to survive – and thrive.

“We have identified a previously undescribed function for the transcription factor FOXP2 in breast cancer,” explains senior author Antoine Karnoub, PhD, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School.

“We have found that depressed FOXP2 [a member of the forkhead family of transcriptional regulators] and elevated levels of its upstream inhibitor microRNA 199a are prominent features of clinically advanced breast cancers that associate with poor patient survival.”

Karnoub’s lab investigates the roles that mesenchymal stem cells (MSCs) play in the development and metastasis of breast cancer. MSCs are adult progenitor cells that function as the body’s early responders, poised to take action to help repair damaged tissues, jumping from their niches in the bone, for example, into the blood, migrating to areas of inflammation, and orchestrating the body’s reactions during wound healing.

Previous work by Karnoub revealed that MSCs respond to breast tumors akin to the way they react to a wound or infection and that these cells participate in the formation of the breast tumor stroma, the supporting network of cells and their secretions that exist in the microenvironment of cancer cells.

“We think that by direct actions on the cancer cells and by manipulating other cells in the microenvironment, MSCsend up providing cancer cells with better abilities to survive and a safe haven in which to thrive,” says Karnoub. Despite expanding knowledge of the role of MSCs to breast malignancy, the underlying molecular responses of breast cancer cells to MSC influences has not been fully delineated. In this new paper, the investigators set out to specifically identify the role that microRNAs were playing in the process.

miRNAs are short noncoding RNAs that play critical functions in cancer pathogenesis,. “An expanding body of evidence has documented miRNA deregulation in multiple aspects of tumor development, including invasion and metastasis,” says Karnoub.

The induction by MSCs of one such miRNA, miR199a, facilitated the acquisition of malignant properties by the cancer cells, including cancer stem cell and metastatic traits. (Cancer stem cells are thought to be the most virulent cells that lie within the core of most tumors, and are believed to be responsible for the resurgence of tumors following chemotherapy treatment.)

“After we found that miRNA-199a instigated in the cancer cells by MSCs was indeed promoting these cancer stem cells phenotypes and was facilitating cancer metastasis, we probed the mechanistic details of miR-199a’s actions, “ explains Karnoub.

“miRNAs function predominantly by suppressing target mRNA expression, and we analyzed an overwhelming majority of the published targets that have been associated with these miRNAs, but none was repressed in our systems. We then made a screen and serendipitously fished out a gene called FOXP2.” At that time, he adds, basically nothing was known about this protein in relation to breast cancer.

FOXP2 has primarily been implicated in regulating speech and language development and several reports have described functions for this protein in developmental neurogenesis. Additional reports have also linked FOXP2 to tissue development, such as the lung.

“We were curious and wanted to find out the business of FOXP2 in breast cancer,” he adds. “Surprisingly, we found that its suppression in the tumor cells was sufficient to expand cancer stem cell traits and caused the cancer cells to metastasize much more vigorously.”

These findings agreed with similar results in which the authors determined that miR-199a upregulation and FOXP2 repression are prominent features of aggressive clinical breast cancers and represent independent prognostic parameters for overall patient survival.

“We are one step closer to understanding how cells in the tumor microenvironment, such as MSCs, promote the malignancy of neighboring cancer cells,” says Karnoub. “We’re now more closely investigating FOXP2’s potential role as a metastasis suppressor that needs to be downregulated for metastasis to take place.”

Study coauthors include BIDMC investigators Benjamin G. Cuiffo (first author), Antoine Campagne, Evan C. Lien and Manoj K. Bhasin; as well as George W. Bell, Antonio Lembo, Francesca Orso, , Monica Raimo, Summer E. Hanson, Andriy Marusyk, Dorraya El-Ashry, Peiman Hematti, Kornelia Polyak, Fatima Mechta-Grigoriou, Odette Mariani, Stefano Volinia, Anne Vincent-Salomon,and Daniela Taverna.

Coauthors are associated with Institut Curie, France; Whitehead Institute for Biomedical Research; University of Turin and MBC, University of Wisconsin-Madison School of Medicine and Public Health, Dana-Farber Cancer Institute, University of Miami Miller School of Medicine, and University of Ferrara, Italy.

This work was supported, in part, by the Sidney Kimmel Cancer Research Foundation, the Susan G. Komen For The Cure, the American Cancer Society, Compagnia di San Paolo, and Progetto Ricerca Ateneo Torino.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently ranks third in National Institutes of Health funding among independent hospitals nationwide.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance, and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Senior Life and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Bonnie Prescott | newswise

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>