Adenomatous polyposis coli genotype-dependent toll-like receptor 4 activity in colon cancer.

Abstract

Toll-like receptors (TLRs)/NF-κB activation stimulated by lipopolysaccharide (LPS) was associated with diverse biological response in colon cancer, but the underlying mechanism was largely unknown. In the current study, we reported cell proliferation was elevated in adenomatous polyposis coli (APC) mutated- and APC knockdown cell lines, while the proliferation was inhibited in APC wild-type cell lines. Besides, in vivo experiments showed that LPS promoted APC knockdown tumor growth while inhibited proliferation of APC wild type. Further study confirmed that activation of TLRs/NF-κB signaling pathway by LPS cross regulated with APC/GSK-3β/β-catenin pathway, which were depend on APC status of cell lines. Taken together, APC genotypes play a key role in LPS induced different colon cancer biological response by cross-regulating β-catenin and NF-κB, which may provide a novel strategy for carcinogenesis prevention.

• Authors: Feng Wen, Yongmei Liu, Wei Wang, Meng Li, Fuchun Guo, Yaxiong Sang, Qing Qin, Yongsheng Wang, Qiu Li
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 7 Pg. 7761-72 (Feb 16 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26760960 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenomatous Polyposis Coli Protein
• Lipopolysaccharides
• NF-kappa B
• RNA, Small Interfering
• TLR4 protein, human
• Toll-Like Receptor 4
• beta Catenin
• Glycogen Synthase Kinase 3 beta

Topics

• Adenomatous Polyposis Coli Protein (antagonists & inhibitors, genetics, metabolism)
• Animals
• Apoptosis
• Blotting, Western
• Cell Proliferation
• Colonic Neoplasms (genetics, metabolism, pathology)
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Genotype
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• Immunoenzyme Techniques
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Nude
• Mutation (genetics)
• NF-kappa B (metabolism)
• RNA, Small Interfering (genetics)
• Toll-Like Receptor 4 (metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• beta Catenin (metabolism)