气候变化领域集成服务门户(CCPortal): Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis

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DOI	10.1073/pnas.2020490118
	Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis
	Wang R.; Godet I.; Yang Y.; Salman S.; Lu H.; Lyu Y.; Zuo Q.; Wang Y.; Zhu Y.; Chen C.; He J.; Gilkes D.M.; Semenza G.L.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:19
英文摘要	Breast cancer patients with increased expression of hypoxia-inducible factors (HIFs) in primary tumor biopsies are at increased risk of metastasis, which is the major cause of breast cancer-related mortality. The mechanisms by which intratumoral hypoxia and HIFs regulate metastasis are not fully elucidated. In this paper, we report that exposure of human breast cancer cells to hypoxia activates epidermal growth factor receptor (EGFR) signaling that is mediated by the HIF-dependent expression of a disintegrin and metalloprotease 12 (ADAM12), which mediates increased ectodomain shedding of heparin-binding EGF-like growth factor, an EGFR ligand, leading to EGFR-dependent phosphorylation of focal adhesion kinase. Inhibition of ADAM12 expression or activity decreased hypoxia-induced breast cancer cell migration and invasion in vitro, and dramatically impaired lungmetastasis after orthotopic implantation of MDA-MB-231 human breast cancer cells into the mammary fat pad of immunodeficient mice. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cell motility; Invasion; Metastasis; Migration; Tumor microenvironment
语种	英语
scopus关键词	ADAM12 protein; epidermal growth factor receptor; focal adhesion kinase; heparin; hypoxia inducible factor; ADAM12 protein; ADAM12 protein, human; EGFR protein, human; epidermal growth factor receptor; HBEGF protein, human; heparin binding epidermal growth factor; animal cell; animal experiment; Article; breast cancer; cancer cell; cell invasion; cell migration; controlled study; ectodomain shedding; fat pad; female; human; in vitro study; lung metastasis; MDA-MB-231 cell line; metastatic breast cancer; mouse; nonhuman; orthotopic transplantation; priority journal; protein binding; protein domain; protein expression; protein phosphorylation; proteinase inhibition; SCID mouse; signal transduction; animal; breast tumor; cell motion; gene expression regulation; gene knockdown; genetics; hypoxia; lung; lung tumor; metabolism; metastasis; pathology; tumor cell line; tumor microenvironment; ADAM12 Protein; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Movement; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Heparin-binding EGF-like Growth Factor; Humans; Hypoxia; Lung; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Metastasis; Signal Transduction; Tumor Microenvironment
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251190
作者单位	Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
推荐引用方式 GB/T 7714	Wang R.,Godet I.,Yang Y.,et al. Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis[J],2021,118(19).
APA	Wang R..,Godet I..,Yang Y..,Salman S..,Lu H..,...&Semenza G.L..(2021).Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis.Proceedings of the National Academy of Sciences of the United States of America,118(19).
MLA	Wang R.,et al."Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis".Proceedings of the National Academy of Sciences of the United States of America 118.19(2021).