Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

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



WATERS CORPORATION

Channels

Drug Discovery

view channel
Image: Molecular model of the anti-cancer drug 5-fluorouracil (Photo courtesy of Wikimedia Commons).

Novel Microcapsule Approach Reduces Toxic Side Effects of Chemotherapy

Cancer researchers have reduced chemotherapy's toxic side effects by using nanoporous capsules to transport an enzyme to the site of a tumor where it is activated by a selective heating process to convert... Read more

Lab Technologies

view channel
Image: The gene assembly robot, the GeneTheatre (Photo courtesy of Analytik Jena AG).

Genomic Research Laboratories Await New Compact Liquid Handling System

A small footprint benchtop liquid handler that automates multiple gene assembly tasks and associated procedures such as PCR setup is now available for use by biotech and genomic research laboratories.... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

02 Jun 2015 - 03 Jun 2015
15 Jun 2015 - 18 Jun 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.