scholarly journals Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54968 ◽  
Author(s):  
Alessio Papi ◽  
Gianluca Storci ◽  
Tiziana Guarnieri ◽  
Sabrina De Carolis ◽  
Sara Bertoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Carbonic Anhydrase ◽  
Hypoxia Inducible Factor ◽  
Carbonic Anhydrase Ix ◽  
Peroxisome Proliferator ◽  
Breast Cancer Stem Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche

Oncogene ◽  
2012 ◽  
Vol 32 (44) ◽  
pp. 5210-5219 ◽  
Author(s):  
F E Lock ◽  
P C McDonald ◽  
Y Lou ◽  
I Serrano ◽  
S C Chafe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Ix ◽  
Breast Cancer Stem Cells

scholarly journals Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia

Oncogene ◽  
2017 ◽  
Vol 37 (8) ◽  
pp. 1062-1074 ◽  
Author(s):  
F Peng ◽  
J-H Wang ◽  
W-J Fan ◽  
Y-T Meng ◽  
M-M Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Pyruvate Dehydrogenase Kinase ◽  
Breast Cancer Stem Cells ◽  
Poor Overall Survival

Abstract Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.

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