scholarly journals Emodin and rhein decrease levels of hypoxia-inducible factor-1α in human pancreatic cancer cells and attenuate cancer cachexia in athymic mice carrying these cells

Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 88008-88020 ◽  
Author(s):  
Lijuan Hu ◽  
Rui Cui ◽  
Hongyi Liu ◽  
Feng Wang
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cachexia ◽  
Hypoxia Inducible Factor ◽  
Human Pancreatic Cancer ◽  
Athymic Mice ◽  
Hypoxia Inducible Factor 1Α ◽  
Pancreatic Cancer Cells

scholarly journals Mint3 depletion restricts tumor malignancy of pancreatic cancer cells by decreasing SKP2 expression via HIF-1

Oncogene ◽  
2020 ◽  
Vol 39 (39) ◽  
pp. 6218-6230 ◽  
Author(s):  
Akane Kanamori ◽  
Daisuke Matsubara ◽  
Yurika Saitoh ◽  
Yuya Fukui ◽  
Noriko Gotoh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Human Pancreatic Cancer ◽  
Mesenchymal Transition ◽  
Skp2 Expression ◽  
Pancreatic Cancer Cells

Abstract Pancreatic cancer is one of the most fatal cancers without druggable molecular targets. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcriptional factor that promotes malignancy in various cancers including pancreatic cancer. Herein, we found that HIF-1 is accumulated in normoxic or moderate hypoxic areas of pancreatic cancer xenografts in vivo and is active even during normoxia in pancreatic cancer cells in vitro. This prompted us to analyze whether the HIF-1 activator Mint3 contributes to malignant features of pancreatic cancer. Mint3 depletion by shRNAs attenuated HIF-1 activity during normoxia and cell proliferation concomitantly with accumulated p21 and p27 protein in pancreatic cancer cells. Further analyses revealed that Mint3 increased transcription of the oncogenic ubiquitin ligase SKP2 in pancreatic cancer cells via HIF-1. This Mint3-HIF-1-SKP2 axis also promoted partial epithelial-mesenchymal transition, stemness features, and chemoresistance in pancreatic cancer cells. Even in vivo, Mint3 depletion attenuated tumor growth of orthotopically inoculated human pancreatic cancer AsPC-1 cells. Database and tissue microarray analyses showed that Mint3 expression is correlated with SKP2 expression in human pancreatic cancer specimens and high Mint3 expression is correlated with poor prognosis of pancreatic cancer patients. Thus, targeting Mint3 may be useful for attenuating the malignant features of pancreatic cancer.

Sign in / Sign up

Export Citation Format

Share Document