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 Desai said "Using ISG15 and UbcH8 gene knocked-down approach, our recent published and unpublished results explicitly demonstrated that the ISG15 pathway inhibits the ubiquitin-mediated proteasome-dependent protein degradation in breast cancer cells.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 Solving the efficiency of Gram-negative bacteria
22.03.2019 | Harvard University

nachricht Bacteria bide their time when antibiotics attack
22.03.2019 | Rice University

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 taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>