Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells.
BACKGROUND
Toll-like receptors (TLRs) are involved in innate immunity. Overexpression of TLRs has been implicated in various types of cancer including colorectal cancer (CRC). The phosphatidylinositol-3'-kinase (PI3K)/Akt signaling pathway is involved in CRC growth and progression. In this study, we determined whether TLR4 signaling and PI3K/Akt pathway activation occur in CRCs.


METHODS
Human CRCs and adjacent mucosa were evaluated for TLR4 expression. CRC cell lines were treated with lipopolysaccharide (LPS), endogenous TLR4 ligand, to assess Akt phosphorylation.


RESULTS
Human CRCs overexpressed TLR4 compared to matched normal mucosa. Additionally, TLR4 was expressed in CRC cells and LPS treatment increased Akt phosphorylation of TLR4-positive CRCs in a time-dependent manner.


CONCLUSIONS
Our results identify TLR4 expression in human CRCs and activation of PI3K with LPS treatment. These findings suggest possible treatment strategies targeting TLR4 in CRC.
Doan
Hung Q
HQ
Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA.
Bowen
Kanika A
KA
Jackson
Lindsey A
LA
Evers
B Mark
BM
D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt