The role of APC in Wnt/ β-Catenin Pathway In gastric Cancer

Most of signaling pathways play a basic role in controlling of embryonic development and cell proliferation in adult tissues. In recent years, mutations that affected on components in most of these pathways have been linked to a type of human cancer. For example, APC (adenomatosis polyposis coli) is the first of critical gene that mutated in the development of colon cancer, as part of the Wnt signaling pathway is known. Cancer development associated with genetic and epigenetic modifications. Studies show that APC including genes that involved through these modifications in cancer, such as gastric cancer. APC is a tumor suppressor protein that regulates part of the Wnt signaling pathway. The protein binds to I²-Catenin, Axin (a scaffold protein) and Gsk3 (glycogen synthase kinase 3) in the cytoplasm and promoted I²-Catenin phosphorylation via Gsk3. phosphorylated I²-Catenin destroyed by the proteasome and thereby inhibits Wnt signaling pathway. On the other hand APC has a nuclear localization signal (NLS) and nuclear export signal (NES). If in the presence of Wnt signal, accumulates I²-Catenin in cytoplasm enters into nucleus, APC connected to accumulated I²-Catenin in nucleus through binding domains and with its shuttling activity translocated I²-Catenin between nucleus and cytoplasm; therefore regulated level and transcriptional activity of I²-catenin in nucleus. If binding region to I²-Catenin of APC genes is mutated, does not occur Wnt signaling inhibition and caused uncontrolled proliferation of cells that lead to cancer cells. In general APC downregulated Wnt signaling pathway and caused cell proliferation inhibition, which indicates the important role of this protein as a tumor suppressor. In addition, APC is one of the genes that are commonly in gastric cancer hypermethylated and APC promoter hypermethylated helps activation of Wnt middle that is associated with development of gastric adenoma. Above shows that the APC as a tumor suppressor plays an important role in Wnt/I²_Catenin signaling pathway. Mutations in this gene can cause gastric cancer, but removing this gene did not influence in incidence of gastric cancer also involved in the development its.