lithium-chloride and Adenoma

A delicate equilibrium of WNT agonists and antagonists in the intestinal stem cell (ISC) niche is critical to maintaining the ISC compartment, as it accommodates the rapid renewal of the gut lining. Disruption of this balance by mutations in the tumour suppressor gene APC, which are found in approximately 80% of all human colon cancers, leads to unrestrained activation of the WNT pathway

Topics: Adenoma; Adenomatous Polyposis Coli Protein; Animals; Cell Competition; Cell Differentiation; Female; Genes, APC; Glycogen Synthase Kinase 3 beta; Humans; Intestinal Neoplasms; Lithium Chloride; Male; Mice; Mutation; Organoids; Wnt Proteins

Fibroblast growth factor-binding protein (FGF-BP) releases immobilized FGFs from the extracellular matrix and can function as an angiogenic switch molecule in cancer. Here we show that FGF-BP is up-regulated in early dysplastic lesions of the human colon that are typically associated with a loss of adenomatous polyposis coli and up-regulation of beta-catenin. In addition, FGF-BP expression is induced in dysplastic lesions in ApcMin/+ mice in parallel with the up-regulation of beta-catenin. Also, in cell culture studies FGF-BP is induced by beta-catenin through direct activation of the FGF-BP gene promoter. We conclude that FGF-BP is a target gene of beta-catenin.

Topics: Adenoma; Animals; beta Catenin; Carrier Proteins; Colonic Neoplasms; Cytoskeletal Proteins; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Lithium Chloride; Mice; Mice, Inbred C57BL; Promoter Regions, Genetic; RNA, Messenger; Trans-Activators; Transfection; Up-Regulation