Transportome Malfunctions and the Hallmarks of Pancreatic Cancer.

Abstract

Ion channels and transporters (ICT) play important roles in almost all basic cellular processes. During last decades, abundant evidences have been provided that ICT (e.g., Ca²⁺ and K⁺ channels) are notable for regulating physiological pancreatic duct cellular function and deregulation of ICT is closely associated with the widely accepted hallmarks of pancreatic ductal adenocarcinoma (PDAC) such as proliferation, apoptosis resistance, invasion, and metastasis. Hence this review focuses on the role of ICT malfunctions in context with the hallmarks of PDAC. After briefly introducing epidemiology and history of molecular oncology of PDAC and summarizing the recent studies on molecular classification systems, we focus then on the exocrine pancreas as a very active secretory gland which considerably impacts the changes in the ion transport system (the transportome) upon malignant transformation. We highlight multiplicity of ICT members (H⁺ transporters, Ca²⁺, K⁺, Na⁺ and Cl^- channels) and their functional impact in PDAC. We also present some selective therapeutic options to interfere with transportome functions and thereby with key mechanisms of malignant progression. This will hopefully contribute to a better clinical outcome based on improved therapeutic strategies for this still extremely deadly disease.