Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular force field helps cancer cells defend against attack

02.02.2006


UF scientists find weakness in cancer’s armor



Much as the famed starship Enterprise would deploy a deflector shield to evade enemy attack, tumor cells are capable of switching on a molecular force field of their own to fend off treatments aimed at killing them. Now University of Florida researchers have found a chink in their armor.

The cells churn out an enzyme that bonds with a protein, creating a protective barrier that deflects damage from radiation or chemotherapy and promotes tumor cell survival. But in laboratory experiments, UF scientists were able to block the union, and the malignant cells died. The findings are opening new avenues of research that could lead to improved cancer therapies, the researchers report this week in the journal Cancer Research.


"We have found a gene called focal adhesion kinase which is produced at very high levels in human tumors, and our work has shown this makes the tumors more likely to survive as they spread throughout the body and grow," said William G. Cance, M.D., a researcher at the University of Florida Shands Cancer Center and chairman of the department of surgery at UF’s College of Medicine. "It also makes them more resistant to our attempts to kill them. And we’re trying to understand exactly why this gene, which is a small enzyme molecule, is very intimately associated with tumor cell survival."

Focal adhesion kinase, or FAK, is commanding increasing attention and has spawned a flurry of research designed to develop new drug therapies, said Cance, who is known internationally for his genetic investigations of tumor survival. These medicines would prevent FAK from linking with the protein known as vascular endothelial growth factor receptor 3, or VEGFR-3. The protein is tied to the growth of channels in the lymph system that serve as cellular superhighways for cancer spread and is found in breast, colon and thyroid tumors.

Cance and colleagues were the first to pull FAK out of human tumors and to show that human cancers make the molecule in large quantities. In 1996, the team was the first to show that if a tumor is prevented from producing the enzyme it dies. The scientists also have identified some protein receptors FAK binds to; VEGFR-3 is the latest they’ve discovered and represents a "hot area for developing therapeutics," Cance said.

"We’ve shown that if you disrupt this interaction - if you block the binding of these two proteins - the tumor cells are more prone to being killed," he said.

UF researchers identified FAK’s interaction with VEGFR-3 in cell cultures of human breast cancer. Breast cancers that pump out high volumes of FAK and VEGFR-3 are more aggressive tumors, Cance said. The scientists were able to block FAK from binding with VEGFR-3 by introducing a different protein that stopped cancer cells from dividing and caused them to die but spared normal breast cells.

"FAK is a critical molecule, and in the future different ways of targeting either the enzyme itself or targeting the binding between these various proteins will have a major impact on cancer, I believe," Cance said. "We think it’s one of the Achilles’ heels for tumor cells and you can disrupt it in a number of different ways. For example, we might be able to design drugs that mimic this area of binding and disrupt it in patients."

Because normal cells generate much lower levels of FAK than tumor cells do, treatments could be developed to target FAK and VEGFR-3 at dosages markedly less toxic to healthy tissues yet lethal to cancer.

"We have a therapeutic window," said Cance, the study’s senior investigator. "In normal cells we’ve shown you can knock it out and cells can still resist the loss of expression of focal adhesion kinase, whereas the tumor cells use it as one of their major proteins for survival."

UF surgical resident Christopher Garces, M.D., and UF research assistant professors Elena Kurenova, Ph.D., and Vita Golubovskaya, Ph.D., also were involved in the work, funded by the National Cancer Institute.

"We take our patients, we look at their tumors and we try to find clues to why their tumors grow, why their tumors spread, and we look at the various genes and proteins that make their tumors what they are," Cance said. "So from the patient’s standpoint, the more that we can characterize their tumor and understand why it behaves like it does, the greater chance we’ll then be able to go back to the patient with therapeutics, and that laboratory bench to bedside is what our research is all about."

H. Shelton Earp III, M.D., director of the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill, said, "The Cance lab finding follows on their groundbreaking work showing that human tumors survive in part by overexpressing FAK. This current discovery provides an important clue as to how to exploit this overexpression for the therapy of human cancers."

Steven Frisch, a professor of biochemistry and molecular pharmacology at West Virginia University, said the research raises "the compelling possibility of targeting FAK for a novel cancer therapy."

"FAK plays a major role in the survival of tumor cells in their normal attached state, and, when over-expressed or hyperactivated, it opens a molecular gate that allows tumor cells to detach and metastasize," Frisch said. "The Cance lab’s new observations on the VEGFR3-FAK interaction are both of interest for understanding the functions of these two pivotal molecules in cell behavior, as well as sharpening the focus of FAK-based drug discovery efforts to control cancer."

Melanie Fridl Ross | EurekAlert!
Further information:
http://www.ufl.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>