New Function of Gene in Promoting Cancer Found by VCU Researchers

Researchers at Virginia Commonwealth University have discovered that a gene well known for its involvement in tumor cell development, growth and metastasis also protects cancer cells from being destroyed by chemotherapy. By inhibiting the expression of this gene, doctors may have a new viable and effective approach for treating aggressive cancers such as breast, liver and prostate carcinomas, malignant gliomas and neuroblastomas that result from high expression of this cancer-promoting gene.

The new study was reported the week of Nov. 22 in PNAS Early Edition, an online publishing of the latest scientific research by the Proceedings of the National Academy of Sciences. The work was a collaboration among researchers from VCU Massey Cancer Center, the VCU Institute of Molecular Medicine (VIMM), and the Department of Human and Molecular Genetics of the VCU School of Medicine, and was led by Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research at VCU Massey.

The involved gene, AEG-1 (astrocyte elevated gene-1), has been known to directly contribute to cancer cell survival, chemotherapeutic drug resistance and tumor cell progression by regulating diverse intracellular processes. This study reveals for the first time a previously unknown aspect of AEG-1 function by identifying the gene as a potential regulator of protective autophagy, which shields cancer cells from destructive agents and environmental insults and is an important feature that may contribute to AEG-1’s tumor-promoting properties. The research further shows that protective autophagy also contributes to AEG-1’s chemoresistance properties, and that inhibition of AEG-1 enhances tumor cells’ response to chemotherapy.

“Understanding how AEG-1 promotes resistance to chemotherapy and enhances cancer cell survival may lead to treatments that inhibit this gene and its regulated pathways, thereby uncovering potentially new therapeutic targets that can be exploited to enhance the ability of anticancer drugs to fight tumors,” said Fisher, who is also chair of VCU’s Department of Human and Molecular Genetics and director of VIMM. “The potential for translating these findings into beneficial approaches for patients is major, particularly for patients with aggressive cancers that are difficult to treat because of resistance to current therapies.”

Fisher collaborated with colleagues from the VCU Department of Human and Molecular Genetics Sujit K. Bhutia, Ph.D.; Timothy P. Kegelman, M.D., Ph.D., student; Swadesh K. Das, Ph.D.; Belal Azab, Ph.D., student; Zhao-zhong Su, Ph.D.; Seok-Geun Lee, Ph.D.; and Devanand Sarkar, M.B.B.S., Ph.D. Su and Sarkar are also research members of VCU Massey Cancer Center, and Sarkar is a member of VIMM.

This study was supported by grants from the National Institutes of Health, the Samuel Waxman Cancer Research Foundation and the National Foundation for Cancer Research.

EDITOR’S NOTE: A copy of the study is available for reporters on a secure, subscription-based website at www.eurekalert.org.

About VCU and VCU Medical Center

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 226 degree and certificate programs in the arts, sciences and humanities. Sixty-seven of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.

About the VCU Massey Cancer Center

VCU Massey Cancer Center is among the top 4 percent of cancer centers in the country to be designated by the National Cancer Institute to lead and shape America’s cancer research efforts. Working with all kinds of cancers, Massey conducts every form of cancer research, including basic science, translational, clinical and population sciences research; provides state-of-the-art cancer treatments and cutting-edge clinical trials; serves as a vital resource for oncology education, teaching and training; and promotes cancer prevention. Since 1974, Massey has been an internationally recognized center of excellence. Massey provides award-winning cancer care at multiple sites throughout Virginia by leading cancer sub-specialists and offers one of the largest selections of cancer clinical trials as well as a statewide network that brings trials to communities across the commonwealth. Its 1,000-plus researchers, clinicians and staff members are dedicated to improving the quality of human life by discovering, developing, delivering and teaching effective means to prevent, detect, treat and ultimately cure cancer. Visit Massey online atmasseycancercenter.org masseycancercenter.org or call 877-4-MASSEY for more information.