Recent Publications by VICC Researchers
December 18, 2014
Vanderbilt-Ingram Cancer Center is committed to conducting innovative, high-impact, basic, translational and clinical research with the greatest potential for making a difference for cancer patients, today and in the future. Here’s a sampling of work published in peer-reviewed journals by Cancer Center investigators in 2014:
Gene study focuses on breast cancer in East Asian women
A new study in East Asian women has identified three genetic changes linked to an increased risk of breast cancer, published online July 24 in Nature Genetics. While breast cancer is one of the most common malignancies among women worldwide, most studies of the genetic risk factors for the disease have focused on women of European ancestry. Qiuyin Cai, M.D., Ph.D., and colleagues performed a genome-wide association study of 22,780 women with breast cancer, and 24,181 control subjects who were recruited in 14 studies in Asian countries. They found DNA sequence changes in two genes, PRC1 and ZC3H11A, and a change near the ARRDC3 gene were associated with breast cancer risk. These results were also replicated in a large consortium, including 16,003 breast cancer cases and 41,335 control subjects of European ancestry.
Breast tissue growth protein may promote cancer
A protein essential for growth of normal breast tissue also may play a role in breast cancer, reported by Yongliang Huo, Ph.D., and Ian Macara, Ph.D., in Nature Cell Biology on May 25. For the first time, they describe the function of the protein Par3L. If the gene for Par3L is deleted, mammary stem cells in mouse models die, and mammary tissue does not grow. Normally Par3L inhibits another polarity protein called LKB1, which suppresses mammary tissue growth. Without Par3L to tamp down the activity of this protein, LKB1 becomes overactive and stem cells quickly die. If, on the other hand, Par3L is overexpressed, it acts as a tumor promoter by shutting down LKB1 and promoting uncontrolled growth, not only in the breast but in other tissues.
Rising tobacco epidemic in Asia linked to elevated risk of death
A new study led by Wei Zheng, M.D., Ph.D., MPH, estimates that tobacco smoking has been linked to approximately 2 million deaths among adult men and women in Asia in recent years and predicts a rising death toll. Published on April 22 in PLOS Medicine, the research found that among men who had smoked, there was an elevated risk of death from cardiovascular disease (CVD), cancer or respiratory diseases. Men who had smoked were nearly twice as likely to die from cancer, especially lung cancer, but there was also an elevated risk of death from cancers of the head and neck, esophagus, stomach, colorectum, liver, pancreas and bladder. While women in most Asian regions are far less likely to smoke than men, the study also found an increased risk of death from cancer, CVD and respiratory diseases among East Asian women.
Protein’s role in spread of colon cancer studied
Research by Robert Coffey, M.D. (Vanderbilt), Liliana Solnica-Krezel, Ph.D. (Washington University in St. Louis), and colleagues has implicated a protein called PLAC8 in the spread of colon cancer. It is expressed at extremely high levels in aggressive tumors, the researchers reported April 1 in the Journal of Clinical Investigation. Analysis in zebrafish and human tissues by first authors Cunxi Li, M.D., Ph.D., and Haiting Ma, Ph.D., linked overexpression of the PLAC8 gene to unconventional epithelial-to-mesenchymal transition, a process by which cells detach from a tumor and become invasive. Using a new immunofluorescence technology, MultiOmyx, the Coffey lab observed PLAC8 and other markers at the leading edge of a human colorectal tumor, supporting its role in cancer invasion, and suggesting it may have prognostic value.
New lung cancer drug target tracked
Vanderbilt researchers identified a potential new drug target in subtypes of lung cancer that are difficult to treat. The study, published April 8 in the Journal of Clinical Investigation, showed for the first time that the target, a receptor called EPHA2, promotes lung tumor growth by modulating a specific cell survival pathway. In collaboration with colleagues at Harvard Medical School, graduate student Katherine Amato and senior author Jin Chen, M.D., Ph.D., also identified a small molecule compound that blocked the receptor’s activity, killed human lung cancer cells in culture and reduced the size of lung tumors in a mouse model. High expression of the EPHA2 receptor had previously been correlated with overall poor patient survival in lung cancer, but until now the biological mechanism and translational potential of these observations were not known.
Stem cell gene linked to prostate cancer susceptibility
A gene on chromosome 8—in a region of the genome linked to risk for many types of cancer—is particularly associated with prostate cancer susceptibility, Jeffrey Smith, M.D., Ph.D., and colleagues reported March 6 in the American Journal of Human Genetics. The gene is related to a master regulator of embryonic stem cells suggesting that it could promote stem cell-like regeneration to initiate cancer. In their analysis of the chromosome 8 region, the researchers noticed a “retrogene” (a copy of another gene that has reinserted into a different spot in the genome) called POU5F1B. They demonstrated that risk variants in the chromosome 8 region correlated with the expression level of POU5F1B in normal prostate tissue. They also found two sites within the retrogene that were predicted to alter expressed protein in a deleterious way, and that were also associated with prostate cancer risk.
More information about our research at: vicc.org/research