Stem cell factor/c-kit signaling enhances invasion of cells via HIF-1 alpha under normoxic condition

作者：Zhang Min; Ma Qingyong^*; Hu Hengtong; Zhang Dong; Li Junhui; Ma Guodong; Bhat Kruttika; Wu Erxi

来源：Cancer Letters, 2011, 303(2): 108-117.

DOI：10.1016/j.canlet.2011.01.017

• SCF/c-kit
• HIF-1 alpha
• Pancreatic cancer
• Invasion
• Normoxia

The SCF/c-kit signaling plays an important role in invasion of c-kit-expressing tumor cells, however, the molecular mechanisms have not been studied yet. Using a pancreatic cancer model, we demonstrate that SCF/c-kit binding up-regulates the expression of invasion-related genes through the accumulation of HIF-1 alpha Furthermore, the expression of HIF-1 alpha induced by SCF is not dependent on the oxygen level, but rather on both the PI3K/1 alpha Akt and Ras/MEK/ERK signaling pathways. In conclusion, under normoxic conditions, SCF/c-kit binding increases expression of HIF-1 alpha through the PI3K/Akt and Ras/MEK/ERK pathways, and the accumulation of HIF-1 alpha up-regulates expression of invasion-related genes that augment the invasiveness of pancreatic cancer, a fatal cancer. Therefore, our results suggest that the inhibition of both c-kit and HIF-1 alpha may be an effective strategy for pancreatic cancer therapy.

• 出版日期2011-4-28
• 单位西安交通大学