Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1α under normoxic condition.

Abstract

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-1α. Furthermore, the expression of HIF-1α induced by SCF 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, SCF/c-kit binding increases expression of HIF-1α through the PI3K/Akt and Ras/MEK/ERK pathways, and the accumulation of HIF-1α 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-1α may be an effective strategy for pancreatic cancer therapy.

• Authors: Min Zhang, Qingyong Ma, Hengtong Hu, Dong Zhang, Junhui Li, Guodong Ma, Kruttika Bhat, Erxi Wu
• Journal: Cancer letters (Cancer Lett) Vol. 303 Issue 2 Pg. 108-17 (Apr 28 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21320746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Small Interfering
• Recombinant Proteins
• Stem Cell Factor
• Proto-Oncogene Proteins c-kit
• Oxygen

Topics

• Antineoplastic Agents
• Cell Line, Tumor
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Neoplasm Invasiveness
• Oxygen (metabolism)
• Pancreatic Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-kit (metabolism)
• RNA, Small Interfering (metabolism)
• Recombinant Proteins (chemistry)
• Signal Transduction
• Stem Cell Factor (metabolism)