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

• Published in: The American journal of surgery 2007-03, Vol.193 (3), p.331-335
• Main Authors: Greenblatt, David Yü, M.D, Kunnimalaiyaan, Muthusamy, Ph.D, Chen, Herbert, M.D., F.A.C.S
• Format: Article
• Language: English
• Subjects: Adhesion; beta Catenin - metabolism; Carcinoid Tumor - enzymology; Carcinoid Tumor - pathology; Carcinoid Tumor - secondary; Carcinoid tumors; Cell Adhesion; Cell culture; Cell Line, Tumor; Colleges & universities; Enzyme Activation; Gastrointestinal Neoplasms - enzymology; Gastrointestinal Neoplasms - pathology; Humans; Kinases; Metastasis; Neuroendocrine tumors; Proteins; Proto-Oncogene Proteins c-raf - metabolism; Raf-1 signaling; Surgery; Tumors; β-catenin
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2006.09.016

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