Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL
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



Channels

Drug Discovery

view channel
Image: A new micelle delivery system for the protective polyphenols resveratrol and quercetin (mRQ) may have value in cancer chemotherapy (Photo courtesy of Oregon State University).

Micelles Containing Resveratrol and Quercetin Reverse Doxorubicin Cardiotoxicity

Cancer researchers blocked the toxic effects of the cancer drug doxorubicin (DOX) by administering it together with the plant antioxidants resveratrol and quercetin. Although in use for more than 40... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Teva Buys Allergan Generic Business Unit

Teva Pharmaceutical Industries (Petah Tikva, Israel) has bought the Allergan (Irvine, CA, USA) generic drugs business for USD 40.5 billion in cash and stock, solidifying its position as the world's largest generic drug maker. Under the terms of the agreement, Teva will pay USD 33.75 billion in cash and USD 6.... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.