机构：[1]Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院[2]Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205[3]McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205[4]Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205[5]Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205[6]Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205[7]Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205[8]Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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.
基金：
This work was supported
by the Emerson Collective Cancer Research Fund, American Cancer
Society, and the Cindy Rosencrans Fund for Triple-Negative Breast Cancer
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
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最新[2023]版：
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第一作者：
第一作者机构：[1]Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China[2]Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205
通讯作者：
通讯机构：[2]Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205[3]McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205[4]Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205[5]Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205[6]Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205[7]Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205[8]Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205
推荐引用方式(GB/T 7714)：
Lan Jie,Lu Haiquan,Samanta Debangshu,et al.Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment.[J].Proceedings of the National Academy of Sciences of the United States of America.2018,115(41):E9640-E9648.doi:10.1073/pnas.1809695115.
APA：
Lan Jie,Lu Haiquan,Samanta Debangshu,Salman Shaima,Lu You&Semenza Gregg L.(2018).Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment..Proceedings of the National Academy of Sciences of the United States of America,115,(41)
MLA：
Lan Jie,et al."Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment.".Proceedings of the National Academy of Sciences of the United States of America 115..41(2018):E9640-E9648
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