Raf-1 activation in gastrointestinal carcinoid cells decreases tumor cell adhesion.

Background: Gastrointestinal carcinoid tumors are highly metastatic. Activation of the Raf-1 signaling pathway in carcinoid cells results in morphologic changes. These Raf-1-induced structural changes may affect cellular adhesion, thereby altering metastatic potential.

Methods: An estrogen-inducible Raf-1 cell line (BON-raf) was used to study the effects of Raf-1 on cellular adhesion. Cell adhesion was measured before and after Raf-1 induction. Western blot analysis was used to confirm Raf-1 activation and measure levels of an essential adhesion regulator, beta-catenin.

Results: Estrogen treatment of BON-raf cells resulted in Raf-1 activation and a marked decrease (68%) in cell adhesion. In the absence of Raf-1 induction, carcinoid cells expressed high levels of beta-catenin. Raf-1 activation led to decreased expression of beta-catenin.

Conclusions: Raf-1 induction in carcinoid cells results in a significant decrease in adhesion. Furthermore, the important adhesion regulator, beta-catenin, is decreased in activated BON-raf cells. These Raf-1-related changes in adhesion may alter the metastatic phenotype of carcinoid cells.