Enhanced cell motility and invasion of chicken embryo fibroblasts in response to JUN over‐expression

Malignant tumor cells exhibit a number of distinct properties involved not only with deregulated cell proliferation but also enhanced migration and invasion. The Jun oncogene has been well studied in regard to its role in cell proliferation. Many of the target genes deregulated by Jun encode matrix metalloproteases (MMPs) such as MMP1, MMP3 and MMP9. These targets implicate a prominent role for Jun in tumor cell invasion, in addition to its role in growth transformation. To investigate this possibility, we have examined the effect of over‐expression of transforming and non‐transforming versions of Jun on motility and invasion of chicken embryo fibroblasts (CEFs). We found that over‐expression of either form of Jun results in elevated intrinsic cellular motility as well as increased motility in response to several different chemo‐attractants, including 3T3‐conditioned media, basic fibroblast growth factor, hepatocyte growth factor and Matrigel. The capacity of these cells to invade through Matrigel is also elevated as a result of Jun over‐expression. In addition to these effects, CEFs expressing Jun secrete factors that stimulate the motility of a human tongue carcinoma cell line. Our results suggest that Jun plays an important role in the potentiation of cell motility and invasion through multiple mechanisms. Int. J. Cancer 81:404–410, 1999. © 1999 Wiley‐Liss, Inc.