Navigation Links
Unexpected role: EGFR protects cancer cells from starving

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
University of Texas M. D. Anderson Cancer Center

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:
Related Image:
Unexpected role: EGFR protects cancer cells from starving
(Date:11/27/2015)... ... November 27, 2015 , ... According to an article published ... Toronto and the University of British Columbia suggested that laws requiring bicyclists to wear ... explains that part of the reason for the controversial conclusion is that, while helmets ...
(Date:11/27/2015)... ... 2015 , ... The rapid speed at which Americans are ... care is needed, especially with Alzheimer’s, dementia and other cognitive conditions becoming more ... forgotten part of this equation: 80 percent of medical care occurs in the ...
(Date:11/27/2015)... ... November 27, 2015 , ... An inventor, from Hopkinsville, Ky., ... medications at home, so he invented the patent-pending ELECTRONIC M.D. , The ELECTRONIC ... In doing so, it could help to prevent potential overdose situations. As a ...
(Date:11/27/2015)... ... 2015 , ... Lizzie’s Lice Pickers just announced a special promotion that will ... their purchase of lice treatment product. In addition, customers will receive a complimentary head ... “Finding lice is a sure way to ruin the holidays, so we encourage all ...
(Date:11/27/2015)... Viejo, CA (PRWEB) , ... November 27, 2015 , ... ... for use in Final Cut Pro X. With ProSidebar: Fasion, video editors can ... or use ProSidebar as a minimalist title opener. Utilize presets featuring self-animating drop ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... the "2016 Future Horizons and Growth ... Testing Market: Supplier Shares, Country Segment Forecasts, ... their offering. --> ) ... "2016 Future Horizons and Growth Strategies in ...
(Date:11/26/2015)... 2015 Research and Markets ( ) ... Care Market by Type (Dressings, Therapy Devices, Active Wound ... Out-Patient Facility), and Geography - Global Forecast to 2020" ... --> --> The purpose of this ... of the global advanced wound care market. It involves ...
(Date:11/26/2015)... Research and Markets ( ) ... Future Horizons and Growth Strategies in the Italian ... Segment Forecasts, Competitive Intelligence, Emerging Opportunities" report ... --> This new 247-page report ... drug monitoring market, including emerging tests, technologies, instrumentation, ...
Breaking Medicine Technology: