Erxi Wu, assistant professor of pharmaceutical sciences, and Kruttika Bhat, doctoral student in the cellular and molecular program and pharmaceutical sciences, co-wrote the article, "Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1alpha under normoxic condition,” which will be published by Cancer Letters.
According to the authors, the stem cell factor/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, they demonstrate that stem cell factor/c-kit binding up-regulates the expression of invasion-related genes through the accumulation of HIF-1alpha. Furthermore, the expression of HIF-1alpha induced by stem cell factor is not dependent on the oxygen level, but rather on both the PI3K/Akt and Ras/MEK/ERK signaling pathways. In conclusion, under normoxic conditions, stem cell factor/c-kit binding increases expression of HIF-1α through the PI3K/Akt and Ras/MEK/ERK pathways, and the accumulation of HIF-1alpha up-regulates expression of invasion-related genes that augment the invasiveness of pancreatic cancer.
"In this study, we present SCF/c-kit enhances the pancreatic cancer invasion via HIF-1alpha. Pancreatic cancer is a fatal cancer; therefore, our results suggest that the inhibition of both c-kit and HIF-1alpha may be an effective strategy for pancreatic cancer therapy," Wu said.
Cancer Letters is an international journal providing a forum for original and pertinent contributions in cancer research.
Wu lab research interests include tumor therapeutic targets, drug discovery and biomarkers. Wu’s lab has a close collaboration with Qingyong Ma’s lab at Xi’an Jiaotong University, China.