Article
Medicine, Research & Experimental
Daniela Magliulo, Matilde Simoni, Carolina Caserta, Cristina Fracassi, Serena Belluschi, Kety Giannetti, Raffaella Pini, Ettore Zapparoli, Stefano Beretta, Martina Ugge, Eleonora Draghi, Federico Rossari, Nadia Coltella, Cristina Tresoldi, Marco J. Morelli, Raffaella Di Micco, Bernhard Gentner, Luca Vago, Rosa Bernardi
Summary: In this study, the researchers found that HIF2 alpha plays an oncogenic role in AML and is a novel regulator of the differentiation block. Blocking HIF2 alpha, in combination with the differentiation agent ATRA, can promote AML cell differentiation, suggesting a potential therapeutic approach for AML treatment.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Jin-Seon Yook, Mikyoung You, Jiyoung Kim, Ashley M. Toney, Rong Fan, Bhanwar Lal Puniya, Tomas Helikar, Sophie Vaulont, Jean-Christophe Deschemin, Meshail Okla, Liwei Xie, Manik C. Ghosh, Tracey A. Rouault, Jaekwon Lee, Soonkyu Chung
Summary: This study investigates the iron-regulatory network underlying beige adipogenesis, showing that thermogenic stimulus leads to redistribution of iron into beige fat through interplay between adipocyte iron demands and systemic iron liberation. Disruption of systemic iron homeostasis impairs beige fat development, suggesting coordinated interplay between renal hypoxia and hepcidin down-regulation as a key mechanism for activating adaptive thermogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Ashley M. Mello, Tenzin Ngodup, Yusoo Lee, Katelyn L. Donahue, Jinju Li, Arvind Rao, Eileen S. Carpenter, Howard C. Crawford, Marina Pasca di Magliano, Kyoung Eun Lee
Summary: Hypoxia plays a crucial role in promoting the inflammatory phenotype in cancer-associated fibroblasts (CAF) in pancreatic ductal adenocarcinoma (PDAC).
Article
Endocrinology & Metabolism
Xiaoya Zheng, Jiani Ma, Min Hu, Jian Long, Qiang Wei, Wei Ren
Summary: This study evaluated the relationship between HIF2 alpha polymorphisms and glucose metabolism in women with PCOS or UI. The results indicated that infertile women with PCOS had metabolic disturbances and specific HIF2 alpha polymorphisms were associated with the risk of PCOS in Han Chinese population.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Hans-Peter Buchstaller, Ada Sala-Hojman, Matthias Leiendecker, Joachim Albers, Uwe Anlauf, Nina Berges, Liming Dong, Thomas Fuchss, Martina Germann, Tim Knehans, Mireille Krier, Marc Lecomte, Daniel Mueller, Sandra R. R. Mueller, Birgitta Leuthner, Ralph Lindemann, Djordje Musil, Mateusz Nowak, Vivian Reither, Corinna Rettig, Christina E. M. Schindler, Urszula Pakulska, Dieter Spuck, Ansgar Wegener, Adrian Zarebski
Summary: The design, synthesis, and SAR exploration of cycloalkyl[c]thiophenes as novel HIF-2α inhibitors are described. These inhibitors were found to disrupt VEGF-A secretion in cancer cells, prevent Arg1 expression and activity in IL4-stimulated macrophages, and modulate target gene expression in vivo. Overall, these HIF-2α inhibitors provide valuable tools for studying selective HIF-2α inhibition and its impact on tumor biology.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Jinsheng Zhu, Li Zhao, Yadan Hu, Guoqi Cui, Ang Luo, Changlei Bao, Ying Han, Tong Zhou, Wenju Lu, Jian Wang, Stephen M. Black, Haiyang Tang
Summary: This study elucidates the importance of HIF2 alpha in the pathogenesis of pulmonary arterial hypertension, demonstrating the potential of HIF2 alpha-mediated gene sets as a diagnostic tool for distinguishing PAH patients. The study also found significant differences in the expression profiles of HIF2 alpha-mediated gene sets in lung tissues and peripheral blood mononuclear cells between control subjects and PAH patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Esther Arnaiz, Ana Miar, Esther Bridges, Naveen Prasad, Stephanie B. Hatch, Daniel Ebner, Charles H. Lawrie, Adrian L. Harris
Summary: In clear cell renal cell carcinoma, HIF2 alpha drives tumor growth and metastasis, leading to drug resistance. The study found that PT2385 can inhibit HIF2 alpha and reduce cell invasion, but does not affect cell proliferation or clonogenicity. Key differences between targeting a specific protein versus gene silencing were identified, potentially offering new drug targets.
Article
Medicine, Research & Experimental
Yang Kong, Pei-Kang Liu, Yao Li, Nicholas D. Nolan, Peter M. J. Quinn, Chun-Wei Hsu, Laura A. Jenny, Jin Zhao, Xuan Cui, Ya-Ju Chang, Katherine J. Wert, Janet R. Sparrow, Nan-Kai Wang, Stephen H. Tsang
Summary: Iron accumulation leads to cell death and tissue dysfunction, requiring chelation therapy to reduce iron overload. However, the use of the iron chelator deferoxamine (DFO) has been associated with systemic adverse effects, including ocular toxicity. This study identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy and established the upregulation of hypoxia-inducible factor (HIF) 2 alpha and mitochondrial deficit as the underlying mechanisms. Suppression of HIF2 alpha and preservation of mitochondrial function using alpha-ketoglutarate (AKG) protected RPE cells and improved visual function in a patient undergoing DFO-chelation therapy.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Jia-Wei Wu, Hao Hu, Dan Li, Li-Kun Ma
Summary: HIF2 alpha transcriptionally regulates IL-6 expression in cardiomyocytes to provide cardioprotection, and treatment with recombinant IL-6 can rescue mice with HIF2 alpha knockdown, activating the PI3K/Akt and STAT3 signaling pathways.
Article
Oncology
Alessa Fischer, Umberto Maccio, Katharina Wang, Juliane Friemel, Martina A. Broglie Daeppen, Diana Vetter, Kuno Lehmann, Astrid Reul, Mercedes Robledo, Constanze Hantel, Nicole Bechmann, Karel Pacak, Kathrin Zitzmann, Christoph J. Auernhammer, Ashley B. Grossman, Felix Beuschlein, Svenja Noelting
Summary: In pheochromocytomas and paragangliomas, hypoxia upregulates the expression of PD-L1 and HIF-2 alpha, promoting tumor progression and immune microenvironment alterations. Head and neck paragangliomas undergoing embolization show significantly higher expression levels of PD-L1 and HIF-2 alpha, suggesting that targeted treatment using HIF-2 alpha and checkpoint inhibitors may be beneficial.
Article
Cell Biology
Weixiao Huang, Xiong Liu, Yao Zhang, Mingxia Deng, Guangqiang Li, Guo Chen, Li Yu, Lai Jin, Tongzheng Liu, Yijie Wang, Yan Chen
Summary: USP5 is a novel deubiquitinase for HIF2 alpha in breast cancer, interacting with HIF2 alpha to protect it from degradation. USP5 promotes the transcription of HIF2 alpha target genes and its high expression is correlated with poor clinical outcomes in breast cancer patients.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Carcelen, Carlos Velasquez, Veronica Vidal, Olga Gutierrez, Jose L. Fernandez-Luna
Summary: The HIF2 alpha-mediated upregulation of ODZ1 enhances transcriptional control of this migration factor in glioblastoma stem cells under hypoxia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Pan Wang, Sheng Gong, Bin Liao, Jinyu Pan, Junwei Wang, Dewei Zou, Lu Zhao, Shuanglong Xiong, Yangmin Deng, Qian Yan, Nan Wu
Summary: The study demonstrated that in a hypoxic microenvironment, the HIF1 alpha/HIF2 alpha-Sox2 network induced the formation of glioma stem cells through the dedifferentiation of differentiated glioma cells, thus promoting glioma cell chemoresistance. Both HIF1 alpha and HIF2 alpha, as genes upstream of Sox2, regulate the malignant progression of glioma through dedifferentiation. The knockout of HIF1 alpha, HIF2 alpha, and Sox2 in glioma cells under hypoxic conditions led to decreased CD133 and CD15 expression and inhibited sphere formation.
Article
Oncology
Chiami Moyama, Mitsugu Fujita, Shota Ando, Keiko Taniguchi, Hiromi Ii, Seisuke Tanigawa, Naoya Hashimoto, Susumu Nakata
Summary: The study revealed that Stat5b co-localizes with Lgr5 in GBM tissues, and its expression in GSCs is regulated by hypoxia and the Wnt pathway. Inhibition of Stat5b induced apoptosis and blocked entry into S-phase in the cell cycle, suggesting that Stat5b may be a promising therapeutic target for attacking GSCs.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yijie Wang, Xiong Liu, Min Wang, Yu Wang, Shuo Wang, Lai Jin, Min Liu, Jun Zhou, Yan Chen
Summary: This study reveals that UBE3B is an E3 ligase for HIF-2 & alpha; and its depletion inhibits breast cancer progression. UBE3B physically interacts with HIF-2 & alpha; and promotes its polyubiquitination, thereby inhibiting its degradation. UBE3B depletion also inhibits breast cancer cell proliferation, migration, and invasion, and suppresses tumor growth and metastasis.
