About: APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway

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About: APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway
Creator	Li, Jinping Yao, Zhi Fu, Zheng Lu, Rong Jia, Jing Yang, Zixia Zhai, Mengying Zhang, Chenrui Zhou, Lingyi
Source	Medline; PMC
abstract	Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies worldwide and has high morbidity and mortality. Elucidating the molecular mechanisms underlying HCC recurrence and metastasis is critical to identify new therapeutic targets. This study aimed to determine the roles of aminopeptidase N (APN, also known as CD13) in HCC proliferation and metastasis and its underlying mechanisms. We detected APN expression in clinical samples and HCC cell lines using immunohistochemistry, flow cytometry, real-time PCR, and enzyme activity assays. The effects of APN on HCC metastasis and proliferation were verified in both in vitro and in vivo models. RNA-seq, phosphoproteomic, western blot, point mutation, co-immunoprecipitation, and proximity ligation assays were performed to reveal the potential mechanisms. We found that APN was frequently upregulated in HCC tumor tissues and high-metastatic cell lines. Knockout of APN inhibited HCC cell metastasis and proliferation in vitro and in vivo. Functional studies suggested that a loss of APN impedes the ERK signaling pathway in HCC cells. Mechanistically, we found that APN might mediate the phosphorylation at serine 31 of BCKDK (BCKDK(S31)), promote BCKDK interacting with ERK1/2 and phosphorylating it, thereby activating the ERK signaling pathway in HCC cells. Collectively, our findings indicate that APN mediates the phosphorylation of BCKDK(S31) and activates its downstream pathway to promote HCC proliferation and metastasis. Therefore, the APN/BCKDK/ERK axis may serve as a new therapeutic target for HCC therapy, and these findings may be helpful to identify new biomarkers in HCC progression.
has issue date	2020-05-26(xsd:dateTime)
bibo:doi	10.1038/s41419-020-2610-1
bibo:pmid	32457292
has license	cc-by
sha1sum (hex)	cc804e61eaf82a9e1d58b8f3e72e239af6352560
schema:url	https://doi.org/10.1038/s41419-020-2610-1
resource representing a document's title	APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway
has PubMed Central identifier	PMC7249043
has PubMed identifier	32457292
schema:publication	Cell Death Dis
resource representing a document's body	covid:cc804e61eaf82a9e1d58b8f3e72e239af6352560#body_text
is schema:about of	named entity 'ERK' named entity 'APN' named entity 'western blot' named entity 'therapeutic' named entity 'proliferation' named entity 'axis' named entity 'potential' named entity 'serve' named entity 'HCC' named entity 'serine' named entity 'signaling pathway' named entity 'HIGH' named entity 'ROLES' named entity 'SERINE' named entity 'THERAPEUTIC' named entity 'MOLECULAR' named entity 'FLOW CYTOMETRY' named entity 'PROXIMITY LIGATION' named entity 'TISSUES' named entity 'USING' named entity 'FOUND' named entity 'THERAPEUTIC TARGET' named entity 'OUR' named entity 'MEDIATE' named entity 'EXPRESSION' named entity 'UNDERLYING' named entity 'PREVALENT' named entity 'EFFECTS' named entity 'STUDY' named entity 'TUMOR' named entity 'phosphorylating' named entity 'mediates' named entity 'upregulated' named entity 'phosphorylation' named entity 'promote' named entity 'enzyme' named entity 'HCC' named entity 'aminopeptidase N' named entity 'HCC' named entity 'promote' named entity 'This' named entity 'determine' named entity 'APN' named entity 'ERK' named entity 'CD13' named entity 'HCC' named entity 'study' named entity 'vivo' named entity 'real-time PCR' named entity 'APN' named entity 'biomarkers' named entity 'western blot' named entity 'HCC' named entity 'therapeutic targets' named entity 'immunohistochemistry' named entity 'metastasis' named entity 'HCC' named entity 'HCC' named entity 'HCC' named entity 'HCC' named entity 'HCC' named entity 'molecular mechanisms' named entity 'morbidity' named entity 'cells' named entity 'metastatic' named entity 'phosphorylated' named entity 'signaling molecules' named entity 'protein' named entity 'BCKDK' named entity 'metastatic' named entity 'BCAA' named entity 'tumors' named entity 'cytokines'

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