Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

ISG15: A novel therapeutic target to slow breast cancer cell motility

12.01.2012
Interferon-stimulated gene 15 (ISG15), a ubiquitin like protein, is highly elevated in a variety of cancers including breast cancer.

How the elevated ISG15 pathway contributes to tumorigenic phenotypes remains unclear and is the subject of a study published in the January 2012 issue of Experimental Biology and Medicine.

Dr. Shyamal Desai and her co-investigators from the Louisiana State University School of Medicine in New Orleans, the University of Pennsylvania School of Medicine in Philadelphia, and the Robert Wood Johnson School of Medicine in New Jersey report that gene knock-down studies demonstrate that elevated ISG15 pathway results in disruption of the cytoskeletal architecture of breast cancer cells. ISG15 also inhibits degradation of cellular proteins involved in cell motility, invasion, and metastasis, promoting breast cancer cell migration.

Dr. Desai said "Using ISG15 and UbcH8 gene knocked-down approach, our recent published and unpublished results explicitly demonstrated that the ISG15 pathway inhibits the ubiquitin-mediated proteasome-dependent protein degradation in breast cancer cells. We were the first to recognize this antagonizing effect of ISG15 in cancer cells"; however, others are increasingly coming to the same conclusion in their observations that ISG15 conjugation stabilizes cellular proteins.

Dr. Arthur Haas said "Given the crucial role of the ubiquitin/26S proteasome pathway in normal cell homeostasis, one expects that ISG15-induced downregulation of the ubiquitin pathway must contribute to breast tumor cell viability. Concurrently, in this manuscript we demonstrate that ISG15 promotes breast cancer cell migration by inhibiting ubiquitin-mediated degradation of cellular proteins associated with cell motility, invasion and metastasis".

The authors report that the elevated ISG15 pathway results in disruption of the cytoskeletal architecture effecting actin polymerization and formation of focal adhesions in breast cancer cells. Targeted knockdown of both ISG15 and UbcH8 resulted in reconstitution of the cytoskeletal architecture. Dr. Desai said "Disruption of cellular architecture is a hallmark of cancer. The ISG15 pathway is also elevated in a variety of tumors. Our results therefore reveal that the ISG15 pathway which is aberrantly elevated in tumors could disrupt cell architecture and contribute to breast cancer cell motility". "Because the cellular architecture is conserved and the ISG15 pathway is constitutively activated in tumor cells of different lineages, our observations in breast cancer must hold true for many other tumors".

If ISG15 confers motility to tumor cells in vivo, as suggested in this manuscript, then Dr. Desai concludes that "strategies to decrease ISGylation could provide a therapeutic advantage for patients diagnosed with metastatic tumors overexpressing the ISG15 pathway".

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said that "these intriguing studies by Desai and colleagues suggests that modulation of the ISG15 pathway may provide future therapeutic targets for breast cancer and other metastatic tumors".

Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://www.ebmonline.org.

Dr. Shyamal D. Desai | EurekAlert!
Further information:
http://www.sebm.org

More articles from Life Sciences:

nachricht New candidate for raw material synthesis through gene transfer
02.07.2020 | Karlsruher Institut für Technologie (KIT)

nachricht Marine alga from the Kiel Fjord discovered as a remedy against infections and skin cancer
02.07.2020 | Helmholtz Centre for Ocean Research Kiel (GEOMAR)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

Im Focus: A structural light switch for magnetism

A research team from the Max Planck Institute for the Structure of Dynamics (MPSD) and the University of Oxford has managed to drive a prototypical antiferromagnet into a new magnetic state using terahertz frequency light. Their groundbreaking method produced an effect orders of magnitude larger than previously achieved, and on ultrafast time scales. The team’s work has just been published in Nature Physics.

Magnetic materials have been a mainstay in computing technology due to their ability to permanently store information in their magnetic state. Current...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

The lightest electromagnetic shielding material in the world

02.07.2020 | Materials Sciences

Spintronics: Faster data processing through ultrashort electric pulses

02.07.2020 | Information Technology

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

VideoLinks
Science & Research
Overview of more VideoLinks >>>