The Roal Of APC In Wnt/ β-Catenin Pathway In Gastric Cancer

Most of signaling pathways play a basic role in controlling of embryonic development andcell proliferation in adult tissues. In recent years, mutations that affected on components inmost 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 ofcolon cancer, as part of the Wnt signaling pathway is known. Cancer developmentassociated with genetic and epigenetic modifications. Studies show that APC includinggenes that involved through these modifications in cancer, such as gastric cancer. APC is atumor suppressor protein that regulates part of the Wnt signaling pathway. The protein bindsto β-Catenin, Axin (a scaffold protein) and Gsk3 (glycogen synthase kinase 3) in thecytoplasm and promoted β-Catenin phosphorylation via Gsk3. phosphorylated β-Catenindestroyed by the proteasome and thereby inhibits Wnt signaling pathway. On the other handAPC has a nuclear localization signal (NLS) and nuclear export signal (NES). If in thepresence of Wnt signal, accumulates β-Catenin in cytoplasm enters into nucleus, APCconnected to accumulated β-Catenin in nucleus through binding domains and with itsshuttling activity translocated β-Catenin between nucleus and cytoplasm; therefore regulatedlevel and transcriptional activity of β-catenin in nucleus. If binding region to β-Catenin of APCgenes is mutated, does not occur Wnt signaling inhibition and caused uncontrolledproliferation of cells that lead to cancer cells. In general APC downregulated Wnt signalingpathway and caused cell proliferation inhibition, which indicates the important role of thisprotein as a tumor suppressor. In addition, APC is one of the genes that are commonly ingastric cancer hypermethylated and APC promoter hypermethylated helps activation of Wntmiddle that is associated with development of gastric adenoma. Above shows that the APCas a tumor suppressor plays an important role in Wnt/β_Catenin signaling pathway.Mutations in this gene can cause gastric cancer, but removing this gene did not influence inincidence of gastric cancer also involved in the development its.

کلیدواژه ها:

APC ، Wnt Signaling ، β-Catenin ، Gastric Cancer ، Tumor-suppressor