The Roal Of HMGA1 Protein In Wnt/ β-Catenin Pathway In Stomach Cancer

Recently gastric cancer is the second causes of cancer death in humans. Studies showedthat development and progression of gastric cancer relevant closely with chronicinflammation of the stomach and in most cases Wnt/β-catenin signaling pathway.It is typicalof diseases caused by environmental factors and oncogenes. High-mobility group A (HMGA)proteins are oncogene chromatin factors that expressed in undifferentiated tissues andvariety of tumors. This proteins contain DNA-binding domains that through this domainsmediated binding of AT-rich regions of the chromatin and having the ability to modulatetranscription of their target genes by modifying chromatin structure at the promoter and/orenhancers. The members of HMGA family, are including HMGA1 and HMGA2 that have highexpressed during embryonic development and also are involved in the progression andmalignant in human cancers such as stomach cancer. Studies showed that overexpression ofHMGA1 associated β_catenin nuclear accumulation in the tissues of the human stomachcancer, so that with the activation of Wnt/β_catenin signaling pathway increases β_cateninaccumulation in cytoplasm and subsequent be transferred β_catenin to nuclear; in this wayβ_catenin acts as an oncogene and transcription coactivator factor of genes involved incancer and through effect on gene of C-myc oncogenes, induced expression of HMGA1 incells. Data showed that HMGA1 can plays an important role in maintaining and proliferationof gastric cancer cells. Overall, these debates suggested that the expression of HMGA1 playsan important role in maintaining the proliferative activity and tumor formation in humans.Investigations showed, HMGA1 has high expression in a broad range of human cancersincluding stomach cancer and that it associated with the occurrence of metastasis and poorprognoses. So HMGA1 proteins induced likely through oncogenic pathways and contribute tomalignant phenotypes in a cancer-specific Manner.

کلیدواژه ها:

HMGA1 ، Wnt Signaling ، β-catenin ، Gastric Cancer ، Oncogen