The title of the paper is "MAP3K4/CBP-Regulated H2B Acetylation Controls Epithelial-Mesenchymal Transition in Trophoblast Stem Cells."
Triple negative breast cancer (TNBC) is a highly recurrent and metastatic form of breast cancer with poor patient prognosis. It has been shown that TNBC cells become highly motile and invasive of other tissues through a molecular program known as the epithelial-mesenchymal transition or “EMT”. This transition leads to metastasis of the tumor. The study led by Amy Abell and Nicole Vincent Jordan in Gary Johnson’s laboratory in the Department of Pharmacology at the University of North Carolina at Chapel Hill and published in Cell Stem Cell, showed that similar to TNBC, normal tissue stem cells use the same molecular EMT program for organ development. This suggests that breast cancer cells utilize this tissue stem cell molecular program for tumor metastasis. This discovery was made using a unique mouse model of tissue stem cell EMT developed in the Johnson laboratory. Two proteins were identified that regulate the expression of specific genes in tissue stem cells during organ development that control normal EMT. In collaboration with Aleix Prat and Charles Perou in the Lineberger Comprehensive Cancer Center the research team found that the normal tissue stem cell EMT gene set overlaps with the breast cancer gene set predicted to stimulate tumor invasiveness. This significant genetic intersection between tissue stem cells and TNBC has identified previously unrecognized genes that likely contribute to breast cancer metastasis. This newly identified gene signature is currently being investigated in different models of breast cancer with the goal of developing new therapeutic interventions for the treatment of TNBC.
Other UNC coauthors are Aleix Prat, Alicia A. Midland, Nancy L. Johnson, Deborah A. Granger, Piotr A. Mieczkowski, Charles M. Perou, Shawn M. Gomez and Gary L. Johnson. Coauthors at the National Institute of Environmental Health Sciences are Weichung Huang and Leiping Li.
Citation: Cell Stem Cell May 6; 8(5): 525-537, 2011.