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Neddylation blockade induces HIF-1? driven cancer cell migration via upregulation of ZEB1.


ABSTRACT: Neddylation is a process by which NEDD8 is covalently conjugated to target proteins by sequential enzymatic reaction. Its role in cancer cell migration has only been recently acknowledged. Previously in cancer cell migration, the epithelial to mesenchymal transition (EMT) process has been well-known to play an important role in both invasion and metastasis by promoting mesenchymal phenotype in epithelial cells. However, the role of neddylation in the EMT process and its mechanistic details are yet to be elucidated. We recently reported that neddylation plays a crucial role in cancer cell migration through the PI3K-Akt pathway. Here, we report that inhibiting neddylation activates the hypoxia-inducible factor 1? (HIF-1?) through the PI3K-Akt pathway, which eventually regulates the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) in various cancer cell lines. As induction of HIF-1? is known to deteriorate the state of cancer and EMT process is one of the hallmarks of metastasis in cancer, our findings uncover the role of neddylation between HIF-1? and ZEB1.

SUBMITTER: Park JB 

PROVIDER: S-EPMC7585416 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Neddylation blockade induces HIF-1α driven cancer cell migration via upregulation of ZEB1.

Park Jun Bum JB   Seo Jieun J   Park Jong-Wan JW   Chun Yang-Sook YS  

Scientific reports 20201023 1


Neddylation is a process by which NEDD8 is covalently conjugated to target proteins by sequential enzymatic reaction. Its role in cancer cell migration has only been recently acknowledged. Previously in cancer cell migration, the epithelial to mesenchymal transition (EMT) process has been well-known to play an important role in both invasion and metastasis by promoting mesenchymal phenotype in epithelial cells. However, the role of neddylation in the EMT process and its mechanistic details are y  ...[more]

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