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

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

Molecule in Green Tea Used as Carrier for Anticancer Proteins

A molecule that is a key ingredient in green tea can be employed as a carrier for anticancer proteins, forming a stable and effective therapeutic nanocomplex. This new discovery could help to construct better drug-delivery systems. Some cancer treatments depend on medication comprising the therapeutic drug and a carrier... Read more

Lab Technologies

view channel
Image: The UC Santa Cruz Ebola Genome Portal contains links to the newly created Ebola browser and to scientific literature on the deadly virus (Photo courtesy of UCSC).

Ebola Genome Browser Now Online to Help Scientists’ Respond to Crisis

A US genomics institute has just released a new Ebola genome browser to help international researchers develop a vaccine and antiserum to help stop the spread of the Ebolavirus. The investigators led... Read more

Business

view channel

Interest in Commercial Applications for Proteomics Continues to Grow

Increasing interest in the field of proteomics has led to a series of agreements between private proteomic companies and academic institutions as well as deals between pharmaceutical companies and novel proteomics innovator biotech companies. Proteomics is the study of the structure and function of proteins.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.