Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt pathway

• Published in: Digestive diseases and sciences 2007-09, Vol.52 (9), p.2292-2300
• Main Authors: YASUDA, Akira, SAWAI, Hirozumi, TAKAHASHI, Hiroki, OCHI, Nobuo, MATSUO, Yoichi, FUNAHASHI, Hitoshi, SATO, Mikinori, OKADA, Yuji, TAKEYAMA, Hiromitsu, MANABE, Tadao
• Format: Article
• Language: English
• Subjects: Benzamides; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Humans; Imatinib Mesylate; Medical sciences; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Piperazines - pharmacology; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - genetics; Stem Cell Factor - genetics; Stem Cell Factor - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-007-9759-7

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 flow 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.