title: Annexin A6 protein is downregulated in human hepatocellular carcinoma.
abstract: Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis. Accordingly, adiponectin, lysophosphatidylcholine, palmitate, and TGFbeta, all of which have a role in liver injury, do not affect AnxA6 expression in human hepatocytes. Likewise, adiponectin and IL8 do not alter AnxA6 levels in primary human hepatic stellate cells. However, in hepatic tumors of 18 patients, AnxA6 protein levels are substantially reduced compared to nontumorous tissues. AnxA6 mRNA is even increased in the tumors suggesting that posttranscriptional mechanisms are involved herein. Lipidomic analysis shows trends toward elevated cholesteryl ester and sphingomyelin in the tumor samples, yet the ratio of tumor to nontumorous AnxA6 does not correlate with these lipids. The current study shows that AnxA6 is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis.
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Meier
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rein-Fischboeck
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Pohl
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Wanninger
authors.affiliation: Department of Physiology, School of Medical Sciences and Bosch Institute, Sydney Medical School, Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Charles Perkins Centre, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoy
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grewal
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Eisinger
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.|Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Krautbauer
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.affiliation: Regensburg University Hospital, University Children Hospital (KUNO), Regensburg, Germany.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.affiliation: Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany. christa.buechler@klinik.uni-regensburg.de.
authors.forename: Christa
authors.identifier: http://orcid.org/0000-0002-5635-3994
authors.initials: C
authors.lastname: Buechler
mesh_terms: D017317:Annexin A6 / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017317:Annexin A6; D009363:Neoplasm Proteins
keywords: Cirrhosis; Hepatic stellate cells; Hepatocyte; Nonalcoholic fatty liver disease