LSUHSC research finds trigger for breast cancer spread

January 03, 2012

New Orleans, LA - Research led by Shyamal Desai, PhD, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, has discovered a key change in the body's defense system that increases the potential for breast cancer to spread to other parts of the body. The results, reported for the first time, are featured in the January 2012 issue of Experimental Biology and Medicine.

For cancer cells shape matters. All cells contain a protein cytoskeleton that acts as a scaffold determining overall shape and function, the position of the cell within an organ or tissue, and the ability of the cell to communicate with its neighbors to prevent the uncontrolled growth typical of cancer cells. However, cell transformations that result in cancer disrupt the genetic programs of the cell and alter the cytoskeleton, leading to changes in shape, function, and cell communication that produce uncontrolled growth and metastatic spreading of the tumor. Understanding these changes to the normal genetic program of a cell and the consequences that ultimately lead to cancer have been major challenges to cancer biologists.

This research, funded by the National Institutes of Health, found that a cellular defense system called the ISG15 pathway, which is normally involved in fighting bacterial and viral infection, is triggered in breast cancer to disrupt normal cytoskeletal function and increase the possibility that the cancer cells will metastasize, or spread.

"Our findings, for the first time, causally link an alteration in the ISG15 pathway during transformation with metastatic potential," notes Dr. Shyamal Desai, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, "thus providing a novel therapeutic target for future drug discovery."

Cells contain a protein quality control pathway termed the Proteasome that breaks down damaged and unneeded proteins to their component amino acids for recycling. Such proteins are marked for degradation by flagging them with a small protein called Ubiquitin, which is then recognized by the Proteasome. Alterations in the genetic program that controls the Ubiquitin/Proteasome system have been known for some time to cause cell transformation and cancer. More recently, Dr. Desai and her colleagues have demonstrated that, unlike normal cells, transformed cancer cells produce increased amounts of a related control system that marks proteins with another small protein called ISG15.

Previous research reports that the amount of ISG15 is increased in high-grade compared with low-grade cancers. The ISG15 system is normally activated by interferon and is part of an ancient cellular immune response designed to counter bacterial and viral infection. By a still unidentified mechanism, cancer cell transformation activates the ISG15 pathway. Dr. Desai and colleagues have previously reported that activation of the ISG15 system interferes with function of the Ubiquitin/Proteasome pathway. In their latest work, Dr. Desai and colleagues show that several key proteins that regulate cell movement, invasion, and metastasis are blocked from Proteasome degradation by the ISG15 system and that genetic manipulation to inhibit this pathway reverses cancer cell transformation, suggesting an approach to blocking cancer progression.

Arthur Haas, PhD, the Roland Coulson Professor and Chairman of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, discovered the ISG15 pathway and co-discovered the Ubiquitin/Proteasome system that was awarded the 2004 Nobel Prize in Chemistry. "These results provide a functional link between the Ubiquitin and ISG15 pathways that reveals how small cell alterations can yield large overall consequences for cell transformation."

The research team also included Arthur Haas, PhD, and Dr. Desai's lab members Ryan Reed, Surendran Sankar, PhD, and Julian Burks in the LSUHSC Department of Biochemistry and Molecular Biology, Jerome Breslin, PhD, in the LSUHSC Department of Physiology, and Ashok Pullikuth, PhD, in the LSUHSC Department Pharmacology, as well as scientists at the UMDNJ-Robert Wood Johnson Medical School in New Jersey, and the University of Pennsylvania School of Medicine in Philadelphia.

"Although this current project focused on breast cancer, ISG15 is also elevated in a variety of cancers," concludes Dr. Desai. "Therefore, this discovery has important implications in other cancers as well."
-end-
LSU Health Sciences Center New Orleans educates Louisiana's health care professionals. The state's academic health leader, LSUHSC consists of a School of Medicine, the state's only School of Dentistry, Louisiana's only public School of Public Health, the only School of Nursing within an academic health center in Louisiana, and Schools of Allied Health Professions, and Graduate Studies. LSUHSC faculty take care of patients in public and private hospitals and clinics throughout the region. In the vanguard of biosciences research in a number of areas in a worldwide arena, the LSUHSC research enterprise generates jobs and enormous economic impact. LSUHSC faculty have made lifesaving discoveries and continue to work to prevent, advance treatment, or cure disease. To learn more, visit http://www.lsuhsc.edu and http://www.twitter.com/LSUHSCHealth.

Louisiana State University Health Sciences Center

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.