HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

Zhang Huimin; Lu Haiquan; Xiang LishaBullen John W.Zhang ChuanzhaoSamanta DebangshuGilkes Daniele M.He JianjunSemenza Gregg L.

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HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

机译：HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

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Increased expression of CD47 has been reported to enable cancer cells to evade phagocytosis by macrophages and to promote the cancer stem cell phenotype, but the molecular mechanisms regulating CD47 expression have not been determined. Here we report that hypoxia-inducible factor 1 (HIF-1) directly activates transcription of the CD47 gene in hypoxic breast cancer cells. Knockdown of HIF activity or CD47 expression increased the phagocytosis of breast cancer cells by bone marrow-derivedmacrophages. CD47 expression was increased in mammosphere cultures, which are enriched for cancer stem cells, and CD47 deficiency led to cancer stem cell depletion. Analysis of datasets derived from thousands of patients with breast cancer revealed that CD47 expression was correlated with HIF target gene expression and with patient mortality. Thus, CD47 expression contributes to the lethal breast cancer phenotype that is mediated by HIF-1.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第45期|E6215-E6223|共9页
作者
Zhang Huimin; Lu Haiquan; Xiang LishaBullen John W.Zhang ChuanzhaoSamanta DebangshuGilkes Daniele M.He JianjunSemenza Gregg L.;
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作者单位

Xi An Jiao Tong Univ, Hlth Sci Ctr, Affiliated Hosp 1, Dept Breast Surg, Xian 710061, Shaanxi, Peoples R China;

Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA;

Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21205 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
antitumor immunity; immune evasion; tumor-initiating cells; tumor microenvironment; "don't eat me" signal;

HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

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