Overexpression of ankyrin1 promotes pancreatic cancer cell growth

// Noriyuki Omura 1 , Masamichi Mizuma 1 , Anne MacGregor 1 , Seung-Mo Hong 1 , Michael Ayars 1 , Jose Alejandro Almario 1 , Michael Borges 1 , Mitsuro Kanda 1 , Ang Li 1 , Audrey Vincent 1 , Anirban Maitra 1, 2 , Michael Goggins 1, 2, 3 1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA 2 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA 3 Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA Correspondence to: Michael Goggins, email: mgoggins@jhmi.edu Keywords: pancreatic cancer, ANK1, hypomethylation, ankyrin, mir-486 Received: February 13, 2016 Accepted: April 10, 2016 Published: April 26, 2016 ABSTRACT The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas. ANK1 was co-expressed with miR-486 in pancreatic cancer cells. Stable knockdown of ANK1 in the pancreatic cancer cell line AsPC1 led to changes in cell morphology, and decreases in colony formation. Stable knockdown of ANK1 also marked reduced the growth of tumors in athymic nude mice. Among patients undergoing pancreaticoduodenectomy, those with pancreatic cancers expressing ANK1 had a poorer prognosis than those without ANK1 expression. These findings indicate a role for ANK1 overexpression in mediating pancreatic cancer tumorigenicity.