Tuesday 1st April 2014
Lorry I. Lokey Stem Cell Building
265 Campus Drive, G3055
Stanford, CA 94305-5461
Elisa Giovannetti, MD, PhD
Associate Professor of Pharmacology
VU University Medical Center, Amsterdam
Role of CYB5A in pancreatic cancer prognosis and modulation of autophagy
Loss of 18q22.3 is a prognostic marker in pancreatic ductal adenocarcinoma (PDAC). Here we evaluate all genes encoded by 18q22.3, and demonstrate that CYB5A RNA and protein expression correlated with survival radically-resected and metastatic patients.
Further, we characterize a novel function to CYB5A, i.e. autophagy induction, as demonstrated by PCR and kinase arrays, as well as by network analysis suggesting CYB5A interaction with TRAF6. TRAF6 expression was reduced after CYB5A reconstitution in cells and in a genetically and histopathologically characterized patient-derived orthotopic mouse model.
CYB5A upregulation decreased tumor dimension and metastasis, as monitored with bioluminescent-imaging and MRI. These results define CYB5A as a novel prognostic factor for PDAC, possibly exerting its tumor-suppressor function via autophagy induction.