title: HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells.
abstract: Hypoxia-inducible factor 1α (HIF-1α) expression is a hallmark of intratumoral hypoxia that is associated with breast cancer metastasis and patient mortality. Previously, we demonstrated that HIF-1 stimulates the expression and activity of TAZ, which is a transcriptional effector of the Hippo signaling pathway, by increasing TAZ synthesis and nuclear localization. Here, we report that direct protein-protein interaction between HIF-1α and TAZ has reciprocal effects: HIF-1α stimulates transactivation mediated by TAZ and TAZ stimulates transactivation mediated by HIF-1α. Inhibition of TAZ expression impairs the hypoxic induction of HIF-1 target genes, such as PDK1, LDHA, BNIP3 and P4HA2 in response to hypoxia, whereas inhibition of HIF-1α expression impairs TAZ-mediated transactivation of the CTGF promoter. Taken together, these results complement our previous findings and establish bidirectional crosstalk between HIF-1α and TAZ that increases their transcriptional activities in hypoxic cells.
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Lisha
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Gilkes
authors.affiliation: Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Hu
authors.affiliation: Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Luo
authors.affiliation: Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Bullen
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
authors.affiliation: Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014162:Transfection
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human
keywords: MCF-7 cells; MDA-MB-231 cells; breast cancer progression; hypoxia-inducible factor 1