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

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jun Bum Park ◽  
Jieun Seo ◽  
Jong-Wan Park ◽  
Yang-Sook Chun
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Enzymatic Reaction ◽  
Akt Pathway ◽  
Cancer Cell Migration ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition

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 1α (HIF-1α) 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-1α 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-1α and ZEB1.

scholarly journals Interleukin-1βAffects MDAMB231 Breast Cancer Cell Migration under Hypoxia: Role of HIF-1αand NFκB Transcription Factors

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Irene Filippi ◽  
Fabio Carraro ◽  
Antonella Naldini
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Cancer Cell Migration ◽  
Breast Cancer Cell Migration

Inflammation and tumor hypoxia are intimately linked and breast cancer provides a typical example of an inflammation-linked malignant disease. Indeed, breast cancer progression is actively supported by inflammatory components, including IL-1β, and by the hypoxia-inducible factor- (HIF-) 1α. In spite of many attempts where the role of either IL-1βor HIF-1αwas evaluated, detailed mechanisms for their effects on breast cancer cell migration under hypoxia are still unclear. We here report that IL-1βincreased MDAMB231 cell migration under hypoxic conditions along with HIF-1αaccumulation and upregulation of CXCR1, which is transcriptionally regulated by HIF-1α, as well as an increased expression of CXCL8 and NFκB. In addition, IL-1β-induced cell migration in hypoxia was not affected when HIF-1αwas inhibited by either siRNA or Topotecan, well known for its inhibitory effect on HIF-1α. Of interest, HIF-1αinhibition did not reduce NFκB and CXCL8 expression and the reduction of IL-1β-induced cell migration under hypoxia was achieved only by pharmacological inhibition of NFκB. Our findings indicate that inhibition of HIF-1αdoes not prevent the migratory program activated by IL-1βin hypoxic MDAMB231 cells. They also suggest a potential compensatory role of NFκB/CXCL8 pathway in IL-1β-induced MDAMB231 cell migration in a hypoxic microenvironment.

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