Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Protein Complex May Play Role in Preventing Many Forms of Cancer, Study Shows

Published: Tuesday, May 07, 2013
Last Updated: Tuesday, May 07, 2013
Bookmark and Share
Researchers at the Stanford University School of Medicine have identified a group of proteins that are mutated in about one-fifth of all human cancers.

The finding suggests that the proteins, which are members of a protein complex that affects how DNA is packaged in cells, work to suppress the development of tumors in many types of tissues.

The broad reach of the effect of mutations in the complex, called BAF, rivals that of another well-known tumor suppressor called p53. It also furthers a growing notion that these so-called chromatin-regulatory complexes may function as much more than mere cellular housekeepers.

"Although we knew that this complex was likely to play a role in preventing cancer, we didn't realize how extensive it would be," said postdoctoral scholar Cigall Kadoch, PhD. "It's often been thought that these complexes play supportive, maintenance-like roles in the cell. But this is really changing now."

Kadoch shares lead authorship of the study with postdoctoral scholar Diana Hargreaves, PhD. Gerald Crabtree, MD, professor of developmental biology and of pathology, is the senior author of the study, published online May 5 in Nature Genetics.

Chromatin-regulatory complexes work to keep DNA tightly condensed, while also granting temporary access to certain portions for replication or to allow the expression of genes necessary for the growth or function of the cell.

Members of Crabtree's laboratory have been interested in BAF complexes and their function for many years. Recently, they reported in the journal Nature that switching subunits within these complexes can convert human fibroblasts to neurons, which points to their instructive role in development and, possibly, cancer.

"Somehow these chromatin-regulatory complexes manage to compress nearly two yards of DNA into a nucleus about one one-thousandth the size of a pinhead," said Crabtree, who is also a member of the Stanford Cancer Institute and a Howard Hughes Medical Institute investigator. "And they do this without compromising the ability of the DNA to be replicated and selectively expressed in different tissues — all without tangling. In 1994 we reported that complexes of this type were likely to be tumor suppressors. Here we show that they are mutated in nearly 20 percent of all human malignancies thus far examined."

The researchers combined biochemical experiments with the data mining of 44 pre-existing studies to come to their conclusions, which would not have been possible without the advent of highly accurate, genome-wide DNA sequencing of individual human tumor samples. Interestingly, mutations to certain subunits, or particular combinations of mutations in the complex's many subunits, seem to herald the development of specific types of cancer — favoring the development of ovarian versus colon cancer, for example.

The importance of the BAF complex as a tumor suppressor is further emphasized by the fact that, in some cases, a mutation in one subunit is sufficient to initiate cancer development.

"For example," said Kadoch, "a type of mutation called a chromosomal translocation in the gene encoding one of these newly identified subunits, SS18, is known to be the hallmark of a cancer called synovial sarcoma. It is clearly the driving oncogenic event and very often the sole genomic abnormality in these cancers." Kadoch and Crabtree published a study in March in Cell uncovering the mechanism and functional consequences of BAF complex perturbation in synovial sarcoma.

The startling prevalence of mutations in the BAF complex was discovered when Kadoch conducted a series of experiments to determine exactly which proteins in the cell were true subunits of the complex. (The exact protein composition of the large complex varies among cell types and species.) Kadoch used an antibody that recognized one core component to purify intact BAF complexes in various cell types, including embryonic stem cells and skin, nerve and other cells. She then analyzed the various proteins isolated by the technique.

Using this method, Kadoch identified seven proteins previously unknown to be BAF components. She and Hargreaves then turned to previously published studies in which the DNA from a variety of human tumors had been sequenced to determine how frequently any of the members of the complex were mutated.

The results, once the newly discovered members were included, were surprising: 19.6 percent of all human tumors displayed a mutation in at least one of the complex's subunits. In addition, for some types of cancers (such as synovial sarcoma), every individual tumor sample examined had a mutation in a BAF subunit. The results suggest that the BAF complex, when unmutated, plays an important protective role against the development of cancer in many different tissues.

The researchers are now focused on learning how the mutations affect the tumor-suppressing activity of the BAF complex.

"We certainly want to further our understanding of the mechanism behind these findings," said Hargreaves. "Do they promote cancer development by inhibiting the proper progression of the cell cycle? Or perhaps they affect how the complex is positioned on the DNA. We'd like to determine how to recapitulate some of these mutations experimentally to see what types of defects they introduce into the complex."

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 2,700+ scientific posters on ePosters
  • More than 3,800+ 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 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

Combination Drug Therapy Shrinks Pancreatic Tumors In Mice
Two drugs that affect the structure and function of DNA have been found to block the growth of pancreatic tumor cells in mice, researchers hope the drugs can soon be tested in humans with the disease.
Thursday, September 24, 2015
Key Mechanism in Gene Expression Discovered
RNA polymerase II makes life possible by expressing genes. Now, a team of Stanford biologists, chemists and applied physicists has observed it at work in real time.
Thursday, September 17, 2015
Scientists Home In On Origin Of Human, Chimpanzee Facial Differences
A study of species-specific regulation of gene expression in chimps and humans has identified regions important in human facial development and variation.
Monday, September 14, 2015
Identifying Defective Heart Genes
A new technique could eventually enable doctors to diagnose genetic heart diseases by rapidly scanning more than 85 genes known to cause cardiac anomalies.
Thursday, August 13, 2015
DNA Damage Seen in Patients Undergoing CT Scanning
Along with the burgeoning use of advanced medical imaging tests over the past decade have come rising public health concerns about possible links between low-dose radiation and cancer.
Monday, July 27, 2015
Genetic Signature Enables Early, Accurate Sepsis Diagnosis
Systemic inflammation after injuries or surgery can dramatically alter the activity of thousands of genes, but a new study shows that changes in just 11 of them are enough to detect the presence or absence of accompanying infection.
Monday, May 18, 2015
Existing Drug May Treat Deadliest Childhood Brain Tumor
For the first time, scientists have identified an existing drug that slows the growth of the deadliest childhood brain tumor.
Friday, May 08, 2015
Foreign Antibodies Mobilize Immune System to Fight Cancer
A mouse’s T cells can be primed to attack and eliminate a malignant tumor by injecting antibodies from another mouse with resistance to the tumor, as well as by activating certain signaling cells, a study has found.
Thursday, May 07, 2015
Tiny Fish Makes Big Splash In Aging Research At Stanford
Researchers disabled aging-associated genes in the short-lived African killifish, including one for an enzyme called telomerase, whose absence caused humanlike disease in the animal.
Friday, February 13, 2015
Tumor Suppressor Also Inhibits Key Property Of Stem Cells
The retinoblastoma protein inhibits cancer by controlling cell division. Now, researchers have shown that it also binds to and inhibits genes necessary for pluripotency.
Friday, November 14, 2014
Scientists Discern Signatures of Old Versus Young Stem Cells
A chemical code scrawled on histones determines which genes in that cell are turned on and which are turned off.
Wednesday, July 03, 2013
Antibody Hinders Growth of Gleevec-Resistant Gastrointestinal Tumors in Lab Test
An antibody that binds to a molecule on the surface of a rare but deadly tumor of the gastrointestinal tract inhibits the growth of the cancer cells in mice.
Thursday, February 07, 2013
Stanford Launches New Center to Advance 'Information Age of Genomics'
With a new research center, Stanford scientists from across campus will join a new "information age of genomics." The goal is nothing short of improving human well-being.
Tuesday, December 04, 2012
Stanford Biologists Watch RNA Fold in Real Time
Using optical tweezers and sub-nanoscale precision, Steven Block and Kirsten Frieda follow the process – and the consequences – of RNA folding.
Monday, October 22, 2012
Where Chromosomes Agree, Stanford researchers Trace Human History
Examining shared stretches of genome from dozens of world populations, Stanford biologists have found a new way, not only to find signatures of human migrations and marriage practices, but to help find hidden disease genes.
Monday, August 20, 2012
Scientific News
Removing 62 Barriers to Pig–to–Human Organ Transplant in One Fell Swoop
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Gene Editing Could Enable Pig-To-Human Organ Transplant
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Antioxidants Cause Malignant Melanoma to Metastasize Faster
Fresh research at Sahlgrenska Academy has found that antioxidants can double the rate of melanoma metastasis in mice.
UC San Diego Team Up with Illumina to Speed-Read Your Microbiome
Data analysis app accelerates studies aimed at using microbes to predict, diagnose and treat human diseases.
Paving the Way for Diamonds to Trace Early Cancers
Researchers from the University of Sydney reveal how nanoscale 'diamonds' can light up early-stage cancers in MRI scans.
Researchers Develop Classification Model for Cancers Caused by KRAS
Most frequently mutated cancer gene help oncologists choose more effective cancer therapies.
Chromosomal Chaos
Penn study forms basis for future precision medicine approaches for Sezary syndrome
Shaking Up the Foundations of Epigenetics
Researchers at the Centre for Genomic Regulation (CRG) and the University of Barcelona (UB) published a study that challenges some of the current beliefs about epigenetics.
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
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
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos