BACKGROUND: The high mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in the development and progression of many malignant neoplasms. High expression of HMGA2 in gastric cancer correlates with invasiveness of cancer and is an independent prognostic factor. The reason for this might be HMGA2 promoting epithelial-mesenchymal transitions (EMT), which is the key process of metastasis for some underlying mechanisms. AIMS: This study was designed to test whether HMGA2 participates in the EMT and to further understand the underlying mechanisms of EMT promoted by HMGA2. METHODS: We examined the cell biology and molecular biology changes after overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To further understand the underlying mechanisms of EMT promoted by HMGA2, based on our previous study, we examined the changes of target genes of HMGA2 after overexpression and knockdown HMGA2 of gastric cancer cells. RESULTS: The results indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of gastric epithelial origin cell in vitro and in vivo. Furthermore, our study showed that HMGA2 was able to elicit EMT and regulate several genes which are closely related to the Wnt/β-catenin pathway by directly binding to their promoter thereby activating the Wnt/β-catenin pathway. CONCLUSIONS: The Wnt/β-catenin pathway activated by HMGA2 might be the underlying mechanism of EMT in gastric cancer cells.
BACKGROUND: The high mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in the development and progression of many malignant neoplasms. High expression of HMGA2 in gastric cancer correlates with invasiveness of cancer and is an independent prognostic factor. The reason for this might be HMGA2 promoting epithelial-mesenchymal transitions (EMT), which is the key process of metastasis for some underlying mechanisms. AIMS: This study was designed to test whether HMGA2 participates in the EMT and to further understand the underlying mechanisms of EMT promoted by HMGA2. METHODS: We examined the cell biology and molecular biology changes after overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To further understand the underlying mechanisms of EMT promoted by HMGA2, based on our previous study, we examined the changes of target genes of HMGA2 after overexpression and knockdown HMGA2 of gastric cancer cells. RESULTS: The results indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of gastric epithelial origin cell in vitro and in vivo. Furthermore, our study showed that HMGA2 was able to elicit EMT and regulate several genes which are closely related to the Wnt/β-catenin pathway by directly binding to their promoter thereby activating the Wnt/β-catenin pathway. CONCLUSIONS: The Wnt/β-catenin pathway activated by HMGA2 might be the underlying mechanism of EMT in gastric cancer cells.
Authors: Chao Chen; Yan Wei; Michael Hummel; Thomas K Hoffmann; Manfred Gross; Andreas M Kaufmann; Andreas E Albers Journal: PLoS One Date: 2011-01-27 Impact factor: 3.240