气候变化领域集成服务门户(CCPortal): HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation

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DOI	10.1073/pnas.2109144118
	HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation
	Liu X.; Xie P.; Hao N.; Zhang M.; Liu Y.; Liu P.; Semenza G.L.; He J.; Zhang H.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:44
英文摘要	Calreticulin (CALR) is a multifunctional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding, and cancer progression. However, the role of CALR in breast cancer (BC) is unclear. Here, we report that CALR is overexpressed in BC compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24-CD44+ cells, and aldehyde dehydrogenase-expressing cells, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation andmetastasis and enhanced chemosensitivity in vivo. Chromatin immunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic BC cells. CALR expression was correlated with Wnt/ β-catenin pathway activation, and an activator of Wnt/β-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALR facilitates BC progression by promoting the BCSC phenotype through Wnt/β-catenin signaling in an HIF-1-dependent manner and suggest that CALR may represent a target for BC therapy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Breast cancer stem cell; Chemosensitivity; EMT; Hypoxia-inducible factors
语种	英语
scopus关键词	aldehyde dehydrogenase; beta catenin; calreticulin; CD24 antigen; Hermes antigen; hypoxia inducible factor 1; Wnt protein; aldehyde dehydrogenase; beta catenin; CALR protein, human; calreticulin; CTNNB1 protein, human; HIF1A protein, human; hypoxia inducible factor 1; hypoxia inducible factor 1alpha; animal cell; animal experiment; animal model; animal tissue; Article; breast cancer; breast carcinogenesis; cancer cell culture; cancer growth; cancer mortality; cancer stem cell; canonical Wnt signaling; chemosensitivity; chromatin immunoprecipitation; controlled study; epithelial mesenchymal transition; female; gene knockdown; gene overexpression; human; human cell; in vivo study; luciferase assay; metastasis; mouse; nonhuman; protein expression; transcription initiation; tumor hypoxia; tumor promotion; breast; breast tumor; carcinogenesis; cell proliferation; cell transformation; disease exacerbation; drug effect; gene expression; gene expression regulation; genetics; metabolism; pathology; pathophysiology; physiology; tumor cell line; Wnt signaling; Aldehyde Dehydrogenase; beta Catenin; Breast; Breast Neoplasms; Calreticulin; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Disease Progression; Epithelial-Mesenchymal Transition; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplastic Stem Cells; Wnt Signaling Pathway
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/250999
作者单位	Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Institute for Cell Engineering, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Radiation Oncology, Johns Hopkins University, School of Medicine, Baltimore, ...
推荐引用方式 GB/T 7714	Liu X.,Xie P.,Hao N.,et al. HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation[J],2021,118(44).
APA	Liu X..,Xie P..,Hao N..,Zhang M..,Liu Y..,...&Zhang H..(2021).HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation.Proceedings of the National Academy of Sciences of the United States of America,118(44).
MLA	Liu X.,et al."HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation".Proceedings of the National Academy of Sciences of the United States of America 118.44(2021).