Navigation Links
Unexpected role: EGFR protects cancer cells from starving
Date:5/5/2008

HOUSTON - A growth factor receptor found abundantly on the surface of cancer cells and long known to fuel cancer growth also protects tumor cells from starvation by a newly identified mechanism, researchers at The University of Texas M. D. Anderson Cancer Center report in the May 5 issue of Cancer Cell.

The epidermal growth factor receptor (EGFR) stabilizes another cell membrane protein that channels a constant supply of glucose to cancer cells, saving them from devouring themselves, a team led by Isaiah J. Fidler, D.V.M., Ph.D., professor and chair of M. D. Anderson's Department of Cancer Biology, and Mien-Chie Hung, Ph.D., professor and chair of the department of Molecular and Cellular Oncology.

Their findings could explain why some drugs that target what was previously thought to be EGFR's only role in cancer proliferation have had limited success in patients. Drugs that block EGFR's activation by growth factors - its tyrosine kinase activity -- have gotten response rates in 10 percent to 20 percent of patients across a variety of cancers.

"We show that the receptor is active independent of its kinase activity," Fidler said. "Up until now everyone - including us - focused on kinase, kinase, kinase."

The team shows that EGFR binds to another cell membrane protein called the sodium/glucose co-transporter (SGLT1), protecting SGLT1 from destruction by the cell's proteasome complex, Hung noted. "This complex stabilizes SGLT1 so it continues to transport glucose from the cell membrane into the cell," Hung said.

A "terrific target"

Cancer cells have a high metabolic rate and require more glucose to fuel their activities than do normal cells, Fidler said.

"Inhibiting the kinase activity of the receptor does not interfere with EGFR stabilizing SGLT1, allowing cancer cells to maintain intracellular glucose levels," Fidler said. "To destroy tumor cells by depriving them of glucose one needs to interfere with the receptor per se rather than activation of the receptor. Whether we can target EGFR and therefore interfere with SGLT and therefore interfere with intracellular glucose remains to be seen, but it's a terrific target to shoot for."

The team concludes that it may be necessary to knock down both EGFR's glucose-related role and its growth-inducing kinase activity in order to attack cancers of the epithelium - tissue that lines the surfaces and cavities of the body's organs. Epithelial cancers, or carcinomas, make up 80 percent of all cancers.

EGFR resides on the surface of cell membranes, where epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-a) can bind to the receptor, launching a molecular phosphorylation cascade, which stimulates the cell to divide. This normal tyrosine kinase activity is put on overdrive in cancer cells because EGFR is heavily overexpressed on the cell's surface.

Block EGFR and cancer cells die of self-cannibalization

In the current research, the team looked at expression of EGFR but not its kinase activity. They found that blocking expression of the receptor with small interfering RNA killed prostate cancer cells. The cells did not die from apoptosis - programmed cell death that forces a defective cell to commit suicide by destroying its DNA complex and its energy-producing mitochondria.

Rather, these cells died of autophagy - a self-cannibalization response in which a cell under stress or lacking nutrients devours part of its cytoplasm and other organelles to survive. When this response goes on long enough, the cell essentially eats itself until it dies. In cancer research, autophagy is thought to be a second type of programmed cell death.

This self-eating response was also seen in breast cancer and colon cancer cells.

Next, the team measured glucose levels in two sets of prostate cancer cells - one treated by a tyrosine kinase inhibitor and the other with EGFR knocked down by siRNA. Glucose levels were unaffected by the tyrosine kinase inhibitor but fell by 50 percent in the cells with EGFR blocked. The results held in breast and colon cancer cells.

Increasing the level of glucose in the medium that held the cells halted autophagic cell death. These results pointed the team toward glucose transporting proteins. They found that when EGFR was knocked down in a cell, levels of SGLT1 also fell as did glucose levels, resulting in autophagic cell death.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Osteotech Announces the Unexpected Passing of Audit Committee Member Leads to Receipt of Nasdaq Deficiency Letter
2. An unexpected way to cause leukemia
3. Longer flu season and unexpected strains make prevention plan key
4. LA BioMed researcher says unexpected increase in cancer risk found
5. Leicester scientist announces unexpected and exciting advance in study of cancer type
6. Men Are Vein Too: Innovative Treatment Sparks Unexpected Consumer Trend
7. Health effects of pesticide mixtures: Unexpected insights from the salmon brain
8. How to Survive an Unexpected Trip to the Hospital During Christmas and New Years
9. Treating Stomach Infection Early Protects Against Cancer
10. Gene Variant Protects Black Heart Failure Patients
11. New Drug Protects Against Radiation Damage
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Unexpected role: EGFR protects cancer cells from starving
(Date:5/24/2017)... ... 24, 2017 , ... Myers Jackson is well known for auctioning homes that ... homes anywhere on the planet. The luxury home market is alive and well and ... A quick search of “11 Spyglass Hill Auction will enlighten you on the dynamics ...
(Date:5/24/2017)... ... May 24, 2017 , ... Accordant Technology, a ... portfolio. ExtraHop delivers an analytics-first approach, layered with machine learning, that provides real-time ... datacenter to the cloud to the edge. Through the new partnership, customers get ...
(Date:5/24/2017)... ... May 24, 2017 , ... The CFOs ... hospitals and health systems in the nation and help their organizations navigate the ... organizations and been instrumental in developing successful hospital and health system strategy. , ...
(Date:5/23/2017)... ... May 23, 2017 , ... MDLand International (MDLand), a leading ... that its iClinic V12.2 solution has achieved approval from National Center for Quality ... 2017 standards which emphasize team-based care with a significant focus on the care ...
(Date:5/23/2017)... ... May 23, 2017 , ... Cambridge, MA, ... steady since 2009, according to a Workers Compensation Research Institute (WCRI) study, a ... the North Carolina System: CompScope™ Benchmarks, 17th Edition looks at indemnity and ...
Breaking Medicine News(10 mins):
(Date:5/9/2017)... 2017  Demonstrating its commitment to representing research- ... the Pharmaceutical Research and Manufacturers of America (PhRMA) ... will now have to meet new research and ... to join PhRMA. "By putting in ... a clear message that being a member of ...
(Date:5/6/2017)... 2017   Provista , a proven leader in the ... today announced Jim Cunniff as the company,s new ... business experience to Provista, including most recently serving as the ... California . He assumed his new role with Provista ... fit for Provista," says Jody Hatcher , president, Sourcing ...
(Date:5/4/2017)... Clarius Mobile Health, a digital healthcare ... this week at the American Congress of Obstetricians ... San Diego, CA from May ... perfect tool for clinicians to easily confirm pregnancy, ... pregnancy-related complications like ectopic pregnancy and placenta previa," ...
Breaking Medicine Technology: