Navigation Links
Enzyme that flips switch on cells' sugar cravings could be anti-cancer target

Cancer cells tend to take up more glucose than healthy cells, and researchers are increasingly interested in exploiting this tendency with drugs that target cancer cells' altered metabolism.

Cancer cells' sugar cravings arise partly because they turn off their mitochondria, power sources that burn glucose efficiently, in favor of a more inefficient mode of using glucose. They benefit because the byproducts can be used as building blocks for fast-growing cells.

Scientists at Winship Cancer Institute of Emory University have shown that many types of cancer cells flip a switch that diverts glucose away from mitochondria. Their findings suggest that tyrosine kinases, enzymes that drive the growth of several types of cancer, play a greater role in mitochondria than previously recognized.

The results also highlight the enzyme PDHK (pyruvate dehydrogenase kinase) as an important point of control for cancer cell metabolism.

The results were published online Thursday by the journal Molecular Cell.

Video available at

"We and others have shown that PDHK is upregulated in several types of human cancer, and our findings demonstrate a new way that PDHK activity is enhanced in cancer cells," says Jing Chen, PhD, associate professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. "PDHK is a very attractive target for anticancer therapy because of its role in regulating cancer metabolism."

Chen and Sumin Kang, PhD, assistant professor of hematology and medical oncology at Emory University School of Medicine, are co-corresponding authors. Postdoctoral fellows Taro Hitosugi, Jun Fan and Tae-Wook Chung are co-first authors of the paper. Co-authors at Emory include Georgia Chen, PhD, Sagar Lonial, MD, Haian Fu, PhD, and Fadlo Khuri, MD. Collaborators at Yale University, Novartis and Cell Signaling Technology contributed to the paper.

Chen and his colleagues started out studying the tyrosine kinase FGFR1, which is activated in several types of cancer. Tyrosine kinases attach a phosphate to other proteins, making them more or less active. They found that FGFR1 activates the enzyme PDHK, which has a gatekeeper function for mitochondria.

"We used FGFR1 as a platform to look at how metabolic enzymes are modified by oncogenic tyrosine kinases," Chen says. "We discovered that several oncogenic tyrosine kinases activate PDHK, and we found that many of those tyrosine kinases are found within mitochondria."

This was a surprise because tyrosine kinases are usually thought to drive growth by being active next to the cell membrane, Chen says.

Introducing a form of PDHK that is insensitive to tyrosine kinases into human cancer cells forces the cells to grow more slowly and form smaller tumors in mice, they found. This indicates that PDHK could be a target for drugs that specifically target cancer cells' altered metabolism.

The experimental drug dichloroacetate (DCA), which inactivates PDHK, is being used in new clinical trials for cancer. Chen is collaborating with Haian Fu, professor of pharmacology and director of the Emory Chemical Biology Discovery Center, to find other, more potent inhibitors of PDHK.


Contact: Lynne Anderson
Emory University

Related medicine news :

1. Regulatory enzyme overexpression may protect against neurodegeneration in Huntingtons disease
2. An enzyme in fish can demonstrate environmental toxins
3. Live-action films of worm sperm help researchers track critical fertility enzymes
4. Researchers identify enzyme that regulates degradation of damaged proteins
5. High-fat diet and lack of enzyme can lead to heart disease in mice
6. Inhibiting key enzymes kills difficult tumor cells in mice
7. Disorderly enzyme is key for antibody diversity
8. New Delhi metallo-beta-lactamase-1 enzyme acquired in Canada
9. Enzyme may drive breast cancer growth
10. Study suggests enzyme crucial to DNA replication may provide potent anti-cancer drug target
11. The TET1 enzyme steers us through fetal development and fights cancer
Post Your Comments:
Related Image:
Enzyme that flips switch on cells' sugar cravings could be anti-cancer target
(Date:6/27/2016)... ... June 27, 2016 , ... recently awarded their highest ... . , Millions of individuals in the United States and Canada wear eyeglasses. Once ... to both correct vision and make a fashion statement. Even celebrities use glasses as ...
(Date:6/26/2016)... ... ... On June 10-11, 2016, A Forever Recovery, a holistic treatment center for ... Table in Battle Creek, MI, where the rehabilitation facility is located. This annual celebration ... world’s leading providers of cereal and other breakfast foods. Its residents often refer to ...
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements owned ... developed to enhance the health of felines. The formula is all-natural and is made ... in the PawPaws Cat Kidney Support Supplement Soft Chews are Astragalus Root ...
(Date:6/26/2016)... Orion, Clarkston, Michigan (PRWEB) , ... June 26, ... ... with respect to fertility once they have been diagnosed with endometriosis. These women ... intercourse but they also require a comprehensive approach that can help for preservation ...
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs ... College of Mohs Surgery and to Dr. Russell Peckham for medical and surgical dermatology. ... treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Research and Markets has announced the addition of ... their offering. The current ... environment for MedImmune to enter. The US ageing population creates ... drive considerable growth for effective anti-influenza medications. The introduction of ... but development is still in its infancy. ...
(Date:6/23/2016)... Ill. and BOGOTA, Colombia , June 23, 2016  Astellas today announced the establishment ... Astellas Farma Brasil as the company,s second affiliate in Latin America . ... ... General Manager of Astellas Farma Colombia ... ...
(Date:6/23/2016)... 2016 Research and Markets has ... Global Analysis (United States, China, Japan, Brazil, United Kingdom, ... their offering. Surgical ... business planners, provides surgical procedure volume data in a ... an in-depth analysis of growth drivers and inhibitors, including ...
Breaking Medicine Technology: