Navigation Links
Protein pushes breast cancer cells to metastasize
Date:7/9/2014

Using an innovative tool that captures heretofore hidden ways that cells are regulated, scientists at Rockefeller University have identified a protein that makes breast cancer cells more likely to metastasize.

What's more, the protein appears to trigger cancer's spread in part by blocking two other proteins that are normally linked to neurodegeneration, a finding that suggests these two disease processes could have unexpected ties.

The study, which appears in the July 10 issue of Nature, points to the possibility of new cancer therapies that target this "master regulator" that helps set metastasis in motion.

"Although the research is in its very early days, if we learn more about how this regulation works, we may in the future be able to generate drugs that prevent this protein from triggering metastatic disease," says Sohail F. Tavazoie, senior author on the study. Tavazoie is Leon Hess Assistant Professor and head of the Vincent Meyer Laboratory of Systems Cancer Biology at Rockefeller.

During the study, Tavazoie and his colleagues used technology previously developed by first author Hani Goodarzi and co-author Saeed Tavazoie, a professor at Columbia University, to measure a new layer of regulation in cancer cells. In order to understand what triggers cells to become malignant, scientists often look at sequences of DNA, searching for genes which are turned on or off in cancerous cells. But in recent years, they've uncovered many new mechanisms that govern cell activity, including some that act on RNA, the genetic material that helps cells make proteins using instructions encoded in DNA. The special strength of Goodarzi and Saeed Tavazoie's tool is that it doesn't look simply at the sequence of RNAit also looks at its shape.

It turns out, the shape of an RNA molecule matters. Specifically, some segments of messenger RNA form hairpin loops, which create sites for key proteins to bind to and regulate that RNA telling the cell to destroy it, for instance. "These structural differences help determine RNA's fate, by exposing or hiding the binding sites for those key proteins," says Goodarzi.

So Goodarzi and Saeed Tavazoie developed a computer algorithm that scans samples of cancer cells and identifies patterns in the shapes and sequences of RNA. In the current study, the authors applied this algorithm to breast cancer cells. In cells prone to metastasis, for example, the scientists found certain RNA hairpin loops that were overrepresented in the sequences of RNAs targeted for destruction. They then identified a protein that binds to those hairpin sequences TARBP2, known to play a role in the formation of small RNAs known as microRNAs. But here, it appears TARBP2 can also act as a "master regulator" of RNA itself, by binding to multiple sites and causing a suite of changes that lead to metastasis including the destruction of the RNAs that carry those key binding sites. Indeed, they found that TARBP2 is overexpressed in cells prone to metastasizing, as well as in metastatic human breast tumors themselves.

To determine how TARBP2 carries out its effects, the researchers looked at which genes appear to be downregulated in metastatic cell lines, reasoning that TARBP2 may block these disease suppressors. They made two surprising discoveries APP, a protein linked to Alzheimer's disease, and ZNF395, which is associated with Huntington's disease, are both downregulated by TARBP2. Cells prone to metastasis showed higher levels of TARBP2 and lower levels of APP and ZNF395; in cancer cells that tend not to spread throughout the body, the opposite was true.

"This was a surprising finding, because these genes are normally associated with neurodegeneration are now implicated in breast cancer metastasis and progression," says Tavazoie. "It's interesting that these totally disparate disease processes have a potential molecular link. We don't know what that means yet."

In further experiments, they discovered that ZNF395 appears to decrease the expression of genes linked to cancer, while one segment of APP directly inhibits breast cancer's ability to metastasize.

The study raises hopes of new cancer therapies that target this "master regulator," TARBP2. "If we can understand the mechanism by which TARBP2 interacts with RNA, maybe in the future we could generate drugs that prevent it from sitting on RNA structures and shutting down the genes that suppress metastatic disease," says Tavazoie.

Just what these findings say about the relationship between cancer and neurodegeneration two of the most common diseases of old age is still unclear, he adds. "All we can say here is that APP and ZNF395, besides being associated with neurodegeneration, also seem to play a functional role in the progression of breast cancer. We can't really make any statements about why this is it could simply be that breast cancer cells use whatever mechanisms necessary to spread throughout the body, and these genes serve that purpose."

Of course, any future therapies that halt metastasis by blocking TARBP2 will have to sidestep the potential risk of promoting neurodegeneration in the process, cautions Goodarzi. All of that will have to be worked out in the lab, agrees Tavazoie.

Funding for the research was provided in part by the National Institutes of Health and the Department of Defense.


'/>"/>
Contact: Franklin Hoke
fhoke@rockefeller.edu
212-327-8998
Rockefeller University
Source:Eurekalert

Related medicine news :

1. NUS researchers discover novel protein complex with potential to combat gastric cancer
2. Mechanism discovered for attaching an on switch that helps cells accessorize proteins
3. Proteins causing daytime sleepiness tied to bone formation, target for osteoporosis
4. Viral infections, including flu, could be inhibited by naturally occurring protein
5. Fungal protein found to cross blood-brain barrier
6. Mount Sinai researchers identify protein that keeps blood stem cells healthy as they age
7. Atomic structure of essential circadian clock protein complex determined
8. Compounds in saliva and common body proteins may fend off DNA-damaging chemicals
9. Penn study shows how misfolded proteins are selected for disposal
10. RaDAR guides proteins into the nucleus
11. TSRI scientists catch misguided DNA-repair proteins in the act
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... Brooklyn, NY (PRWEB) , ... June 27, 2016 ... ... is using cutting edge technology to revolutionize the emergency ambulance transport experience for ... Many are aware of how Uber has disrupted the taxi industry through the ...
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements owned by ... to enhance the health of felines. The formula is all-natural and is made from ... the PawPaws Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract ...
(Date:6/25/2016)... ... 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due to ... a new, often overlooked aspect of head lice: the parasite’s ability to live away from ... common occurrence, but a necessary one in the event that lice have simply gotten out ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, ... at Work award to iHire in recognition of their exemplary accomplishments in worksite health ... annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. Her ... would lash out at his family verbally and physically. , “When something upset him, he ... he would use it. He would throw rocks at my other children and say he ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 24, 2016 According to a ... (Standard Pen Needles, Safety Pen Needles), Needle Length (4mm, ... Hormone), Mode of Purchase (Retail, Non-Retail) - Trends & ... studies the market for the forecast period of 2016 ... 2.81 Billion by 2021 from USD 1.65 Billion in ...
(Date:6/24/2016)... NAMUR , Belgium , ...  (NYSE MKT: VNRX), today announced the appointment of ... Board of Directors as a Non-Executive Director, effective ... the Company,s Audit, Compensation and Nominations and Governance ... Board, Dr. Futcher will provide independent expertise and ...
(Date:6/23/2016)... -- MedSource announced today that it has selected Datatrial,s ... choice.  This latest decision demonstrates MedSource,s commitment to ... by offering a state-of-the-art electronic data capture (EDC) ... the EDC platform of choice in exchange for ... long been a preferred EDC platform by our ...
Breaking Medicine Technology: