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Mol Cell Biochem. 2016 Jul;418(1-2):81-90. doi: 10.1007/s11010-016-2735-9. Epub 2016 Jun 23.

Annexin A6 protein is downregulated in human hepatocellular carcinoma.

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Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.
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.
Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany.
Regensburg University Hospital, University Children Hospital (KUNO), Regensburg, Germany.
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 93042, Germany.


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.


Cirrhosis; Hepatic stellate cells; Hepatocyte; Nonalcoholic fatty liver disease

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