C86
S100A6 binds to annexin 2 and modulates pancreatic cancer cell motility
Taoufik Nedjadi1, Fiona Campbell2, Rosalind E Jenkins3, Neil Kitteringham3, Francisco X Real4, Pilar Navarro4, Alexei Tepikin5, John P Neoptolemos1, Eithne Costello1
1Division of Surgery and Oncology, The University of Liverpool, Liverpool, UK, 2Department of Pathology. The University of Liverpool, Liverpool, UK, 3Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, UK, 4Programa de Patología Molecular Centro Nacional de Investigaciones Oncológicas, Madrid, Spain, 5Department of Physiology, The University of Liverpool, Liverpool, UK
Background
Molecular profiling of pancreatic cancer revealed over-expression of a protein named S100A6. Recently we found an association between elevated levels of S100A6 and poor survival in pancreatic cancer patients. The functional role of S100A6 is however, poorly understood. The aim of the present study was to investigate the functional relevance of S100A6 expression in pancreatic cancer.
Method
A proteomic approach was used to identify S100A6-interacting proteins, and western blot, immunohistochemistry and immunofluorescence were used to validate the findings. siRNA was used to reduce expression of S100A6 and annexin II in pancreatic cancer cells. Cell motility and invasion were assessed using Boyden and Matrigel chambers respectively.
Results
Annexin 11, annexin 2, tropomyosin beta and lamin B1 were identified as S100A6 interacting proteins. Of these, annexin 2 was considered particularly interesting, since like S100A6 it has been shown to be expressed early in the development of pancreatic cancer and overexpression occurs with high frequency in invasive cancer. Analysis of primary pancreatic cancer specimens revealed that 80% of patients expressed both proteins. A strong association was observed between high levels of cytoplamic S100A6 and the presence of annexin 2 in the plasma membrane of cancer cells (P=0.009). Knockdown of S100A6 caused a pronounced reduction in the pancreatic cancer cells motility. A similar reduction in motility was observed following annexin 2 knockdown.
Conclusion
These findings point towards a functional role for S100A6 in pancreatic cancer cell motility that may help explain the link between S100A6 expression in pancreatic cancer and aggressive disease.
