Abstract
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. High mobility group box chromosomal protein 1 (HMGB)-1 is a widely studied, ubiquitous nuclear protein that is present in eukaryotic cells, and plays a crucial role in inflammatory response. However, the effects of HMGB-1 on human chondrosarcoma cells are largely unknown. In this study, we found that HMGB-1 increased the migration and the expression of α5β1 integrin in human chondrosarcoma cells. Transfection of cells with receptor for advanced glycation end products (RAGE) receptor siRNA reduced HMGB-1-induced cell migration and integrin expression. Activations of phosphatidylinositol 3-kinase (PI3K), Akt, and AP-1 pathways after HMGB-1 treatment were demonstrated, and HMGB-1-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and AP-1 cascades. Taken together, our results indicated that HMGB-1 enhances the migration of chondrosarcoma cells by increasing α5β1 integrin expression through the RAGE receptor/PI3K/Akt/c-Jun/AP-1 signal transduction pathway.
Original language | English |
---|---|
Pages (from-to) | 98-106 |
Number of pages | 9 |
Journal | Cancer Letters |
Volume | 322 |
Issue number | 1 |
DOIs | |
Publication status | Published - Sept 1 2012 |
Keywords
- Chondrosarcoma
- HMGB-1
- Integrin
- Migration
- RAGE
ASJC Scopus subject areas
- Oncology
- Cancer Research