Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
PZ HTL SA
GLOBETECH PUBLISHING

Disruption of Mitochondrial Enzyme Function Characterizes Some Cancers

By BiotechDaily International staff writers
Posted on 02 Jan 2012
Since mutations in the genome of cancer cells often force tumors to use metabolic pathways not found in normal cells, cancer researchers believe that drugs targeting these pathways will be able to destroy tumors with fewer adverse side effects.

Some tumors harbor mutations in the citric acid cycle (CAC or Krebs cycle) or electron transport chain (ETC) that disable normal oxidative mitochondrial function. In this regard investigators at Emory University (Atlanta, GA, USA) studied the relationship between the enzyme PDHK1 (pyruvate dehydrogenase kinase 1), an important point of control for cancer cell metabolism, and the tyrosine kinase FGFR1 (fibroblast growth factor receptor 1), which is activated in several types of cancer.

They reported in the December 23, 2011, online edition of the journal Molecular Cell that tyrosine phosphorylation enhanced PDHK1 kinase activity by promoting ATP and pyruvate dehydrogenase complex (PDC) binding. Functional PDC formed in mitochondria outside of the matrix in some cancer cells.

Expression of a mutant, nonfunctional form of PDHK1 in cancer cells led to decreased cell proliferation under hypoxia and increased oxidative phosphorylation with enhanced mitochondrial utilization of pyruvate and reduced tumor growth in xenograft nude mice.

“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,” said senior author Dr. Jing Chen, associate professor of hematology and medical oncology at Emory University School. “PDHK is a very attractive target for anticancer therapy because of its role in regulating cancer metabolism. We used FGFR1 as a platform to look at how metabolic enzymes are modified by oncogenic tyrosine kinases. We discovered that several oncogenic tyrosine kinases activate PDHK, and we found that many of those tyrosine kinases are found within mitochondria.”

The experimental drug dichloroacetate (DCA), which inactivates PDHK, is being evaluated in clinical trials while researchers continue to seek other, more potent inhibitors of PDHK.

Related Links:
Emory University



Channels

Drug Discovery

view channel
Image: Chitosan is derived from the shells of shrimp and other sea crustaceans, including Alaskan pink shrimp, pictured here (Photo courtesy of NOAA - [US] National Oceanic and Atmospheric Administration).

Chitosan Treatment Clears the Way for Antibiotics to Eliminate Recurrent Urinary Tract Infections

Recurrent urinary tract infection was successfully resolved in a mouse model by treatment with the exfoliant chitosan followed by a round of antibiotics. Bacterial urinary tract infection (UTI), most... Read more

Biochemistry

view channel

Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases. The researchers plan to begin human trials late 2014. The study, which was published December... Read more

Therapeutics

view channel

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients. Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may... Read more

Business

view channel

Analytical Sciences Trade Fair Declared a Rousing Success

Organizers of this year's 24th "analytica" biosciences trade fair have reported significant increases in both the number of visitors and exhibitors compared to the 2012 event. The analytica trade fair for laboratory technology, analysis, and biotechnology has been held at the Munich (Germany) Trade Fair Center every... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.