Navigation Links
ISG15: A novel therapeutic target to slow breast cancer cell motility
Date:1/11/2012

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 Desai said "Using ISG15 and UbcH8 gene knocked-down approach, our recent published and unpublished results explicitly demonstrated that the ISG15 pathway inhibits the ubiquitin-mediated proteasome-dependent protein degradation in breast cancer cells.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".


'/>"/>
Contact: Dr. Shyamal D. Desai
sdesai@lsuhsc.edu
Society for Experimental Biology and Medicine
Source:Eurekalert

Related biology news :

1. Researchers discover novel anti-viral immune pathway in the mosquito
2. Chinese herbal medicine may provide novel treatment for alcohol abuse
3. Autism may be linked to abnormal immune system characteristics and novel protein fragment
4. Novel device removes heavy metals from water
5. Barracuda babies: Novel study sheds light on early life of prolific predator
6. Scientist-novelist back with second book at cell biology meeting
7. University Hospitals Seidman Cancer Center tests novel drug that makes brain tumors glow hot pink
8. New study identifies novel role for PEA-15 protein in cancer growth
9. Novel monoclonal antibody offers potential treatment for tumors resistant to VEGF therapy
10. Benefit of novel drug in breast cancer seen in blood within weeks
11. Novel technique switches triple-negative breast cancer cells to hormone-receptor positive cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/1/2016)... , Feb. 1, 2016  Wocket® smart wallet ( www.wocketwallet.com ) announces ... personality, Joey Fatone . Las Vegas , ... --> Las Vegas , where Joey appeared ... The new video ad was filmed at the Consumer Electronics Show ... the Wocket booth to meet and greet fans. ...
(Date:1/25/2016)... 25, 2016  Glencoe Software, the world-leading supplier of ... industries, will provide the data management solution OMERO Plus ... Photo - ... Phenotypic analysis measures the characteristics and ... comparisons between states such as health and disease, the ...
(Date:1/20/2016)... Jan. 20, 2016 A market that just ... benefit from the explosion in genomics knowledge. Learn all ... Research. A range of dynamic trends are pushing market ... personalized medicine - pharmacogenomics - pathogen evolution - next ... markets - greater understanding of the role of genetic ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... ... February 09, 2016 , ... Tunnell Consulting, Inc. announced that Frédéric Lefebvre ... will focus on acquiring new accounts and work closely with existing Tunnell clients throughout ... brings to our European clients more than 15 years of experience in the pharmaceutical ...
(Date:2/9/2016)... This market research report on the global ... of the market in terms of revenue (USD Million). ... the manufacture of microbiology culture media and related products. ... snapshot providing the overall information of various market segments ... also provides the overall information and data analysis of ...
(Date:2/8/2016)... GUELPH, ON , Feb. 8, 2016 /PRNewswire/ - BIOREM ... nominated to the top ten finalists for clean technology companies ... are the top 10 companies listed on the TSX ... mining, oil & gas, clean technology & life ... formula with equal weighting given to return on investment, market ...
(Date:2/8/2016)... ... 2016 , ... Thomas J. Todorow has joined the University ... Corporate Services and the Chief Financial Officer at The Children’s Hospital of Philadelphia ... Care Contracting, Supply Chain, and Investments. , Prior to joining CHOP and The ...
Breaking Biology Technology: