Molecular Determinants of Gastrointestinal and Liver Cancers: Role of Bile Acid Activated Nuclear Receptors

Barbara      Renga; Andrea      Mencarelli; Sabrina      Cipriani; Eleonora      Distrutti

doi:10.2174/156802612799436614

Abstract

Invasion and metastasis are critical determinants of gastrointestinal and liver cancers morbidity. Genes and molecules participating in these steps (e.g. growth factors and their receptors, cell cycle regulators, cell adhesion molecules, matrix degrading enzymes) have been progressively clarified. Activated Wnt signaling pathway has been found in these tumors. Mutations in one of the DNA mismatch repair genes, alterations in epigenetics, such as aberrant DNA methylation and histone modifications are associated with the progression of gastrointestinal and control liver neoplasies. Bile acids (BAs), the main constituents of bile, activate a family of nuclear receptors (NRs) that control critical steps in bile acid homeostasis, endo- and xenobiotics detoxification, glucose, lipid metabolism and innate immunity. BAs activated NRs are misregulated in gastrointestinal and liver cancers. The present review provides an overview on the molecular determinants involved in gastrointestinal and liver cancers and focuses on the role of BAs activated NRs in the pathogenesis of these tumors.

Keywords: Metastatic process, Wnt signaling, gastric carcinoma, colorectal cancer, hepatocarcinoma, Bile acids, Farnesoid X Receptor, Vitamin D Receptor, Pregnane X Receptor, gastrointestinal and liver cancers morbidity, Wnt signaling pathway, Mutations in one of the DNA mismatch repair genes, bile acid homeostasis, lipid metabolism, liver cancers