Understanding how tumors progress from early to later stages is essential for devising appropriate therapies. Thomas Wirth and colleagues, from Ulm University in Germany, used a breast cancer model system to show that a protein called NF-kB, which works in the cell by turning on a variety of other genes, is involved in tumor progression when its activity in the cell is altered. The authors showed that NF-kB is essential for the initial transition stage called epithelial-mesenchymal transition, which is thought to be important for allowing tumors to be able to invade other tissues.
Using a cell line that would undergo this transition when given a growth factor, the authors showed that when NF-kB activity was blocked, these cells could not undergo the transition. Furthermore, if the NF-kB pathway was over-activated, the cells no longer required the addition of the growth factor to transition, but instead would spontaneously undergo the epithelial-mesenchymal transition. Further, inhibiting NF-kB after transition had already occurred caused these cells to revert back to their original state. To test this in a living model, the authors blocked the NF-kB pathway in nude mice that were injected with breast cancer cells.
Under these conditions, these breast cancer cells were unable become metastatic, unlike those that were injected in nude mice where the NF-kB pathway was not blocked. Taken together, these data provide evidence for an essential role of NF-kB in the induction and maintenance of the transition that cancer cells undergo to become invasive and mark the NF-kB pathway as a potential anti-metastatic therapeutic target.
TITLE: NF-kB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression
AUTHOR CONTACT:
Thomas Wirth Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany
Phone: 49-731-500-23270; Fax: 49-731-500-22892; E-mail: thomas.wirth@medizin.uni-ulm.de
View the PDF of this article at: http://www.jci.org/cgi/content/full/114/4/569
Journal of Clinical Investigation