Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
BioConferenceLive

Metastasis Drug Target Identified

By BiotechDaily International staff writers
Posted on 26 Mar 2014
Image: LIMD2, a protein that can drive metastasis (Photo courtesy of the Wistar Institute).
Image: LIMD2, a protein that can drive metastasis (Photo courtesy of the Wistar Institute).
Cancer researchers have identified a protein that is critically linked to processes leading to metastasis, the deadly spread of cancer away from the primary tumor.

Investigators at The Wistar Institute (Philadelphia, PA, USA) examined the role of "LIM domain" proteins in metastasis. LIM domains are protein structural domains, composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker. LIM domain containing proteins have been shown to play roles in cytoskeletal organization, organ development, and oncogenesis. LIM domains mediate protein-to-protein interactions that are critical to cellular processes.

The investigators focused their attention on LIMD2, a mechanistically undefined LIM-only protein originally found to be overexpressed in metastatic lesions but absent in the matched primary tumor.

They determined the solution structure of LIMD2 using nuclear magnetic resonance and reported in the March 2014 issue of the journal Cancer Research that it revealed a classic LIM-domain structure that was highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase-parvin-pinch complex. Structural and biochemical analyses revealed that LIMD2 bound directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Cells that lacked ILK failed to respond to the induction of invasion by LIMD2.
LIMD2 levels in fresh and archival tumors positively correlated with cell motility, metastatic potential, and grade, including bladder, melanoma, breast, and thyroid tumors. LIMD2 directly contributed to these cellular phenotypes as shown by overexpression, knockdown, and reconstitution experiments in cell culture models.

“This is the result of a five year effort to characterize LIMD2, which is a new protein that we found to be expressed only in metastatic lesions, and not in the primary tumor or in normal tissues or organs,” said senior author Dr. Frank Rauscher III, a professor in the tumor microenvironment and metastasis program at The Wistar Institute. “LIMD2 is a great candidate for targeting with a drug, which would inhibit the ability of these cells to leave a primary tumor and to colonize other organs. We contend that LIMD2 is a marker that could help physicians profile tumors, and a potential drug target that could yield a potent therapy for a variety of advanced cancers, perhaps in combination with existing or emerging therapies.”

“Cancer metastasis is really the final frontier in cancer medicine, because metastasis kills,” said Dr. Rauscher. “We can treat a primary tumor, usually successfully, with surgery, drugs, chemotherapy, or radiation, but once the cancer spreads to organs throughout the body it frequently becomes unstoppable.”

Related Links:

The Wistar Institute



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel

Precise Ion Irradiation Dosing Method Developed for Cancer Therapy

Scientists are employing nuclear physics principles to provide more effective approaches to radiotherapy treatment for cancer patients. Radiation therapy using heavy ions is best suitable for cancer patients with tumors that are difficult to access, such as in the brain. These particles scarcely damage the penetrated... Read more

Business

view channel

Cancer Immunotherapy Sector Predicted to Surge to USD 9 Billion Across Major Pharma Through 2022

The immunotherapy market will experience substantial growth through 2022, increasing from USD 1.1 billion in 2012 to nearly USD 9 billion in 2022 (corresponding to 23.8% annual growth) in the United Kingdom, United States, France, Germany, Italy, Spain, and Japan, according to recent market research. This notable growth... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.