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

doi:10.1007/s10620-007-9759-7

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

Dig Dis Sci. 2007 Sep;52(9):2292-300. doi: 10.1007/s10620-007-9759-7. Epub 2007 Apr 5.

Authors

Akira Yasuda¹, Hirozumi Sawai, Hiroki Takahashi, Nobuo Ochi, Yoichi Matsuo, Hitoshi Funahashi, Mikinori Sato, Yuji Okada, Hiromitsu Takeyama, Tadao Manabe

Affiliation

¹ Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan. a-yasuda@med.nagoya-cu.ac.jp

PMID: 17410437
DOI: 10.1007/s10620-007-9759-7

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 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.

MeSH terms

Benzamides
Blotting, Western
Cell Line, Tumor
Cell Proliferation*
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Colorectal Neoplasms* / pathology
Flow Cytometry
Gene Expression Regulation, Neoplastic*
Humans
Imatinib Mesylate
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

Substances

Benzamides
Piperazines
Protein Kinase Inhibitors
Pyrimidines
Stem Cell Factor
Imatinib Mesylate
Phosphatidylinositol 3-Kinases
Protein-Tyrosine Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3