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:11/30/2015)... NC (PRWEB) , ... November 30, 2015 , ... ... Dawes, Amanda Beard and Brooke Bennett are collaborating with brands across various categories ... These four influential figures make up an elite group of Gold Medal Moms ...
(Date:11/30/2015)... City, NY (PRWEB) , ... December 01, 2015 , ... ... as a 2015-2016 inductee into its VIP Woman of the Year Circle. She is ... the nation’s leading networking organization exclusively for professional women, boasting more than 850,000 members ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... stressful. At the VA Maryland Health Care System, the Caregiver Support Program ... “Caregivers have a difficult job. Seventy-four percent report that their role as ...
(Date:11/30/2015)... ... November 30, 2015 , ... According to research ... U.S. require dental technicians to be certified or obtain continuing education. To increase ... “What’s In Your Mouth?” campaign to inform dentists that the technicians they trust ...
(Date:11/30/2015)... ... November 30, 2015 , ... The Museum of Science & ... a new era of publicly accessible automated technology. Now, by popular demand, the ... guests an up-close look at the shuttle at MOSI’s main entrance. This experience ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... 2015 North America was ... grow at a CAGR of 7.6% from 2015 to 2020. ... 135.6 million in 2014, and is expected to grow at a ... to the new Market Research Report "North America Cardiac Output Monitoring ... (Hospitals, ambulatory care, others) - Analysis And Forecast To 2020", the ...
(Date:11/30/2015)... Six Months Ended 30 September 2015 2014RestatedChange%Turnover 545,575 , 518,852 , ... , 384,242 , 9.8 Hospital Management Service ... (18.3) Medical Insurance Administration Service Income , 2,780 ... Devices and Accessories Sales , 89,645 , 94,580 ... 2,822 , 2,917 , (3.3) ...
(Date:11/30/2015)... VIEW, Calif. , Nov. 30, 2015 ... been the norm in U.S. medical imaging ... The increasingly popular accountable care payer-provider contracts ... models and, in their wake, alter provider-vendor ... quality-based payments will push forward new purchasing ...
Breaking Medicine Technology: