scholarly journals Toll-Iike Receptor-3 Activation Enhances Malignant Traits in Human Breast Cancer Cells Through Hypoxia-inducible Factor-1α

2020 ◽  
Vol 40 (10) ◽  
pp. 5379-5391
Author(s):  
FRANCESCA SCATOZZA ◽  
ANTONELLA D'AMORE ◽  
ROSARIA ANNA FONTANELLA ◽  
PAOLA DE CESARIS ◽  
FRANCESCO MARAMPON ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment

2018 ◽  
Vol 115 (41) ◽  
pp. E9640-E9648 ◽  
Author(s):  
Jie Lan ◽  
Haiquan Lu ◽  
Debangshu Samanta ◽  
Shaima Salman ◽  
You Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Adenosine Receptor ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Hypoxia Inducible Factor 1

Breast cancer stem cells (BCSCs), which are characterized by a capacity for unlimited self-renewal and for generation of the bulk cancer cell population, play a critical role in cancer relapse and metastasis. Hypoxia is a common feature of the cancer microenvironment that stimulates the specification and maintenance of BCSCs. In this study, we found that hypoxia increased expression of adenosine receptor 2B (A2BR) in human breast cancer cells through the transcriptional activity of hypoxia-inducible factor 1. The binding of adenosine to A2BR promoted BCSC enrichment by activating protein kinase C-δ, which phosphorylated and activated the transcription factor STAT3, leading to increased expression of interleukin 6 and NANOG, two key mediators of the BCSC phenotype. Genetic or pharmacological inhibition of A2BR expression or activity decreased hypoxia- or adenosine-induced BCSC enrichment in vitro, and dramatically impaired tumor initiation and lung metastasis after implantation of MDA-MB-231 human breast cancer cells into the mammary fat pad of immunodeficient mice. These data provide evidence that targeting A2BR might be an effective strategy to eradicate BCSCs.

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