Medical Research: What is the background for this study? What are the main findings?
Dr. Storz: Our study focuses on cellular signaling mechanisms that lead to the initiation of pancreatic cancer. After acquisition of an oncogenic mutation of Kras, pancreatic acinar cells can undergo a transdifferentiation process to a phenotype that gives rise to pancreatic intraepithelial lesions (PanINs). These lesions then can further progress to pancreatic cancer.
Medical Research: What should clinicians and patients take away from your report?
Dr. Storz: We show that the serine/threonine kinase protein kinase D1 (PKD1) is a key-player in the reprogramming of acinar cells. Using a conditional knockout approach, we find that PKD1 is sufficient to drive acinar cell metaplasia to a ductal phenotype and its progression to pancreatic intraepithelial lesions. Moreover, using 3D explant culture of primary pancreatic acinar cells, we delineate the signaling pathway that is initiated by mutant Kras to activate PKD1; and also identify Notch signaling as downstream target for this kinase.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Storz: Understanding the signaling pathways that regulate reprogramming of acinar cells to a cell type that gives rise to pancreatic precancerous lesions is important for risk prognosis or early diagnosis of pancreatic cancer. Knowledge of these signaling cascades also will lead to identification of pharmacologically targetable signaling molecules (such as PKD1) that will allow prevention of progression, and possibly phenotype reversion.
Inhibition of PKD1 gene may halt pancreatic cancer progression and formation
Geou-Yarh Liou, Heike Döppler, Ursula B. Braun, Richard Panayiotou, Michele Scotti Buzhardt, Derek C. Radisky, Howard C. Crawford, Alan P. Fields, Nicole R. Murray, Q. Jane Wang, Michael Leitges, Peter Storz. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia. Nature Communications, 2015; 6: 6200 DOI: 10.1038/ncomms7200
MedicalResearch.com Interview with: Peter Storz, Ph.D. (2015). Signaling Pathways That Lead Pancreatic Cancer Identified