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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: 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.
Authors: D Franchimont; S Vermeire; H El Housni; M Pierik; K Van Steen; T Gustot; E Quertinmont; M Abramowicz; A Van Gossum; J Devière; P Rutgeerts Journal: Gut Date: 2004-07 Impact factor: 23.059
Authors: Judith H Harmey; Corazon D Bucana; Weixin Lu; Anne Marie Byrne; Susan McDonnell; Conor Lynch; David Bouchier-Hayes; Zhongyun Dong Journal: Int J Cancer Date: 2002-10-10 Impact factor: 7.396
Authors: D Peter O'Leary; Lavinia Bhatt; John F Woolley; David R Gough; Jiang H Wang; Thomas G Cotter; H Paul Redmond Journal: PLoS One Date: 2012-10-11 Impact factor: 3.240