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Dig Dis Sci (2007) 52:22922300 DOI 10.1007/s10620-007-9759-7
ORIGINAL PAPER
Stem Cell Factor/c-kit Receptor Signaling Enhances the Proliferation and Invasion of Colorectal Cancer Cells Through the PI3K/Akt Pathway
Akira Yasuda Hirozumi Sawai Hiroki Takahashi Nobuo Ochi Yoichi Matsuo Hitoshi Funahashi Mikinori Sato Yuji Okada Hiromitsu Takeyama Tadao Manabe
Received: 10 November 2006 / Accepted: 1 January 2007 / Published online: 5 April 2007
C
Springer Science+Business Media, LLC 2007
Abstract In this study, we examined the role of c-kit receptor (KIT) signal transduction on the proliferation and invasion of colorectal cancer cells. We found that c-kit was expressed in 2 colorectal cancer cell lines as determined by RT-PCR, Western blot, and ow cytometry. In KIT-positive lines, KIT was activated by stem cell factor (SCF). SCF enhanced cellular proliferation of positive lines as demonstrated by the WST-1 proliferation assay. Furthermore, SCF enhanced the invasive ability of KIT-positive cell lines. SCF stimulation upregulated p44/42 mitogen-activated protein kinase (MAPK) and Akt as shown by Western blot. We examined the roles played by p44/42 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways in proliferation and invasion. PI3K/Akt activity strongly correlated with proliferation and invasion and p44/42 MAPK was correlated with only invasion. In conclusion, the SCF-enhanced proliferation and invasion of KIT-positive colorectal cancer cells is achieved mainly through the PI3K/Akt pathway.
Keywords c-kit . SCF . Colorectal cancer . PI3K/Akt .
Proliferation . Invasion
The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) closely related to other receptors including platelet-derived growth factor receptor and macrophage growth factor receptor [1]. The primary ligand for KIT is stem cell factor (SCF), which is also known as mast cell growth factor and kit ligand [24]. Binding of SCF to KIT causes
A. Yasuda ([envelopeback]) H. Sawai H. Takahashi N. Ochi Y. Matsuo H. Funahashi M. Sato Y. Okada H. Takeyama T. Manabe Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 4678601 Japan e-mail: [email protected]
dimerization, autophosphorylation, and signal transduction [5]. The SCFKIT signaling system supports the proliferation, differentiation, and survival of KIT-expressing cells, such as hematopoietic progenitors, mast cells, melanocytes, and cells of Cajal [6, 7]. KIT is also expressed in solid tumors and hematologic malignancies, such as gastrointestinal stromal tumor (GIST) [8], small-cell...