Hydroxylase Activity of ASPH Promotes Hepatocellular Carcinoma Metastasis Through Epithelial-to-Mesenchymal Transition Pathway

EBioMedicine
Qifei ZouFeng Shen

Abstract

Over-expression of aspartyl (asparagynal)-β-hydroxylase (ASPH) contributes to hepatocellular carcinoma (HCC) invasiveness, but the role of ASPH hydroxylase activity in this process remains to be defined. As such, the current study investigated the role of ASPH hydroxylase activity in downstream signalling of HCC tumorgenesis and, specifically, metastasis development. Over-expression of wild-type ASPH, but not a hydroxylase mutant, promoted HCC cell migration in vitro, as well as intrahepatic and distant metastases in vivo. The enhanced migration and epithelial to mesenchymal transition (EMT) activation was notably absent in response to hydroxylase activity blockade. Vimentin, a regulator of EMT, interacted with ASPH and likely mediated the effect of ASPH hydroxylase activity with cell migration. The enhanced hydroxylase activity in tumor tissues predicted worse prognoses of HCC patients. Collectively, the hydroxylase activity of ASPH affected HCC metastasis through interacting with vimentin and regulating EMT. As such, ASPH might be a promising therapeutic target of HCC.

Citations

Feb 29, 2020·The Journal of Biological Chemistry·Lennart BrewitzChristopher J Schofield
Jun 21, 2019·Database : the Journal of Biological Databases and Curation·Qingyu LiuXianhua Dai
Aug 20, 2020·Journal of Experimental & Clinical Cancer Research : CR·Madiha KanwalRuth Tachezy
Oct 23, 2020·Nature Reviews. Cancer·Julie-Aurore LosmanWilliam G Kaelin
Apr 23, 2021·Angewandte Chemie·Amelia BrasnettChristopher J Schofield
Jul 6, 2021·Journal of Fluorine Chemistry·Lennart BrewitzChristopher J Schofield
Jul 21, 2021·Metallomics : Integrated Biometal Science·Jenna M GreveJ A Cowan
Jan 9, 2022·Journal of Experimental & Clinical Cancer Research : CR·Qianlei ZhouZhiyu Xiao

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Methods Mentioned

BETA
Assay
Co-Immunoprecipitation
transfection
Tandem Affinity Purification
PCR
nuclear translocation
pull-down
immunoprecipitation

Software Mentioned

SPSS

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