β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma
| Autor: | Joo-Won Jeong, Jae-Sun Choi, Woom-Yee Bae, Seungyoon Nam |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Angiogenesis media_common.quotation_subject Mice Nude Transfection Article Metastasis 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Oxygen homeostasis medicine Animals Humans Internalization Molecular Biology media_common Chemistry Cancer Cell Biology medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit beta-Arrestin 2 Rats Disease Models Animal 030104 developmental biology Apoptosis Tumor progression 030220 oncology & carcinogenesis Cancer research Disease Progression Glioblastoma Function (biology) |
| Zdroj: | Cell Death Differ |
| ISSN: | 1476-5403 |
| Popis: | The basic function of β-arrestin 2 (Arrb2) is to negatively regulate the G-protein-coupled receptor signaling pathway through facilitating receptor desensitization and internalization. Arrb2 has also been reported to play various roles in cancer pathology including the proliferation, migration, invasion, metastasis, and apoptosis of solid tumors. However, the molecular mechanisms underlying the tumorigenic capacities of Arrb2 have not been elucidated. Here, we show a novel function of Arrb2: Arrb2 facilitates the degradation of HIF-1α, which is a master regulator of oxygen homeostasis. We also demonstrate that Arrb2 interacts with HIF-1α and stimulates ubiquitin-mediated 26S proteasomal degradation of HIF-1α by recruiting PHD2 and pVHL. Overexpression of Arrb2 in human glioblastoma cells suppresses HIF-1α signaling, tumor growth, and angiogenesis. Consistent with this antitumorigenic effect of Arrb2, low Arrb2 expression levels correlate with high HIF-1α expression and poor glioblastoma patient survival. These results collectively reveal a novel function of Arrb2 in the oxygen-sensing mechanism that directly regulates HIF-1α stability in human cancers and suggest Arrb2 as a new potential therapeutic target for glioblastoma. |
| Databáze: | OpenAIRE |
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