Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Identify Gene that Controls Aggressiveness in Breast Cancer Cells

Published: Monday, July 08, 2013
Last Updated: Monday, July 08, 2013
Bookmark and Share
Researchers have identified a transcription factor, known as ZEB1, that is capable of converting non-aggressive basal-type cancer cells into highly malignant, tumor-forming cancer stem cells (CSCs).

Intriguingly, luminal breast cancer cells, which are associated with a much better clinical prognosis, carry this gene in a state in which it seems to be permanently shut down.

The researchers, whose findings are published this week in the journal Cell, report that the ZEB1 gene is held in a poised state in basal non-CSCs, such that it can readily respond to environmental cues that consequently drive those non-CSCs into the dangerous CSC state. Basal-type breast carcinoma is a highly aggressive form of breast cancer. According to a 2011 epidemiological study, the 5-year survival rate for patients with basal breast cancer is 76%, compared with a roughly 90% 5-year survival rate among patients with other forms of breast cancer.

“We may have found a root source, maybe the root source, of what ultimately determines the destiny of breast cancer cells—their future benign or aggressive clinical behavior,” says Whitehead Founding Member Robert Weinberg, who is also a professor of biology at MIT and Director of the MIT/Ludwig Center for Molecular Oncology.

Transcription factors are genes that control the expression of other genes, and therefore have a significant impact on cell activities. In the case of ZEB1, it has an important role in the so-called epithelial-to-mesenchymal transition (EMT), during which epithelial cells acquire the traits of mesenchymal cells. Unlike the tightly-packed epithelial cells that stick to one another, mesenchymal cells are loose and free to move around a tissue. Previous work in the Weinberg lab showed that adult cancer cells passing through an EMT are able to self-renew and to seed new tumors with high efficiency, hallmark traits of CSCs.

Other earlier work led by Christine Chaffer, a postdoctoral researcher in the Weinberg lab, demonstrated that cancer cells are able to spontaneously become CSCs. Now Chaffer and Nemanja Marjanovic have pinpointed ZEB1, a key player in the EMT, as a gene critical for this conversion in breast cancer cells.

Breast cancers are categorized into at least five different subgroups based on their molecular profiles. More broadly these groups can be subdivided into the less aggressive ‘luminal’ subgroup or more aggressive ‘basal’ subgroup. The aggressive basal-type breast cancers often metastasize, seeding new tumors in distant parts of the body. Patients with basal breast cancer generally have a poorer prognosis than those with the less aggressive luminal-type breast cancer.

Chaffer and Marjanovic, a former research assistant in the Weinberg lab, studied non-CSCs from luminal- and basal-type cancers and determined that cells from basal cancers are able to switch relatively easily into CSC state, unlike luminal breast cancer cells, which tend to remain in the non-CSC state.

The scientists determined that the difference in ZEB1’s effects is due to the way the gene is marked in the two types of cancers. In luminal breast cancer cells, the ZEB1 gene is occupied with modifications that shut it down. But in basal breast cancer cells, ZEB1’s state is more tenuous, with repressing and activating markers coexisting on the gene. When these cells are exposed to certain signals, including those from TGFß, the repressive marks are removed and ZEB1 is expressed, thereby converting the basal non-CSCs into CSCs.

So what does this new insight mean for treating basal breast cancer?

“Well, we know that these basal breast cancer cells are very plastic and we need to incorporate that kind of thinking into treatment regimes,” says Chaffer. “As well as targeting cancer stem cells, we also need to think about how we can prevent the non-cancer stem cells from continually replenishing the pool of cancer stem cells. For example, adjuvant therapies that inhibit this type of cell plasticity may be a very effective way to keep metastasis at bay.”

Marjnaovic agrees but cautions that the model may not be applicable for every cancer.

“This is an example of how adaptable cancer cells can be,,” says Marjanovic, who is currently a research assistant at the Broad Institute. “We have yet to determine if ZEB1 plays a similar role in all cancer types, but the idea that cancer cells reside in a poised state that enables them to adapt to changing environments may be a mechanism used by many cancers to increase their aggressiveness.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Yeast, Human Stem Cells Drive Discovery of New Parkinson’s Disease Drug Targets
Using a discovery platform whose components range from yeast cells to human stem cells, scientists have identified a novel Parkinson’s disease drug target.
Wednesday, October 30, 2013
Precision Gene Targeting in Stem Cells Corrects Disease-Causing Mutations
Whitehead Institute researchers manipulate targeted genes in both human embryonic stem cells and induced pluripotent stem cells.
Tuesday, July 19, 2011
Whitehead Member Rudolf Jaenisch Honored for Groundbreaking Stem Cell Research
Israel’s Wolf Foundation has named Whitehead Institute Founding Member Rudolf Jaenisch a recipient of the prestigious 2011 Wolf Prize in Medicine.
Friday, February 18, 2011
Embryonic Stem Cells Reveal Oncogene's Secret Growth Formula
Researchers describes a pausing step in the transcription process that serves to regulate expression of as many as 80% of the genes in mammalian cells.
Monday, May 03, 2010
Technique Enables Efficient Gene Targeting In Human Embryonic Stem Cells
Whitehead scientists have developed a technique to modify or introduce genes into the genomes of human ESCs and iPS cells.
Thursday, August 27, 2009
Novel Cell Lines Propel the Search for Safer Stem Cell Induction
Researchers produce mice and mouse cell lines with identical configurations of the specific factors needed to reprogram adult cells to an embryonic-stem-cell-like state.
Thursday, January 22, 2009
Single Virus Used to Convert Adult Cells to Embryonic Stem Cell-Like Cells
Researchers have simplified the creation of induced pluripotent stem cells, cutting the number of viruses used in the reprogramming process from four to one.
Monday, December 22, 2008
Recipe for Cell Reprogramming Adds Protein
A drug-like molecule can be substituted for the cancer gene c-Myc, one of four genes added to adult cells to reprogram them to an embryonic-stem-cell-like state, says Whitehead researchers.
Friday, August 08, 2008
Putting microRNAs on the Stem Cell Map
Whitehead researchers have now discovered how microRNAs fit into the map of embryonic stem cell circuitry.
Friday, August 08, 2008
Scientists Identify Gene that Regulates Polarity in Regenerating Flatworms
Whitehead scientists have discovered that the gene Smed-beta-catenin-1 is required for proper decisions about head-versus-tail polarity in regenerating flatworms.
Monday, December 10, 2007
Reprogrammed Adult Cells Treat Sickle-Cell Anemia in Mice
Mice with a human sickle-cell anemia disease trait have been treated successfully by directly reprogramming their own cells to an embryonic-stem-cell-like state, without the use of eggs.
Monday, December 10, 2007
Adult Stem Cells Lack Key Pluripotency Regulator
A study by Whitehead researcher has shown that protein Oct4 is not required to maintain mouse adult stem cells in their undifferentiated state.
Wednesday, October 17, 2007
How Embryonic Stem Cells Maintain Their Identity
Two studies report details of the "genetic program" that affords embryonic stem cells the flexibility to give rise to any cell type in the body.
Wednesday, April 26, 2006
Scientific News
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
New Material Forges the Way for 'Stem Cell Factories'
Researchers have discovered the first fully synthetic substrate with potential to grow billions of stem cells. The researchcould forge the way for the creation of 'stem cell factories' - the mass production of human embryonic (pluripotent) stem cells.
Liver Regrown from Stem Cells
Scientists have repaired a damaged liver in a mouse by transplanting stem cells grown in the laboratory.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
'Google Maps' for the Body
Scientists have revealed research that uses previously top-secret technology to zoom through the human body down to the level of a single cell that could be a game-changer for medicine.
Adaptimmune's Novel Cancer Therapeutics Show Positive Clinical Trial Results
The company has announced that positive data from its Phase I/II study of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in patients with multiple myeloma has been published.
Stem Cells Rescue Patients from Mitochondrial Disease
A study led by OHSU researchers has revealed a critical first step in developing a new gene and stem cell regenerative technique for treating patients with mitochondrial disease.
Eco-Friendly Nanobullet to Battle Bacteria
Researchers have developed a method to combat bacteria by engineering nanoscale particles that add the antimicrobial potency of silver to a core of lignin, a ubiquitous substance found in all plant cells.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!