Hypoxia‐inducible factor‐1α blocks differentiation of malignant gliomas

摘要: Aberrant differentiation is a characteristic feature of neoplastic transformation, while hypoxia in solid tumors believed to be linked aggressive behavior and poor prognosis. However, the possible relationship between malignancies remains poorly defined. Here we show that rat C6 primary human malignant glioma cells can induced differentiate into astrocytes by well-known adenylate cyclase activator forskolin. hypoxia-inducible factor-1α expression stimulated mimetics cobalt chloride or deferoxamine blocks this effectiveness reversible upon withdrawal mimetics. Importantly, knockdown inducible RNA interference restores capabilities cells, even presence chloride, whereas stabilization through retarded ubiquitination von Hippel-Lindau tumor suppressor gene silence abrogates differentiation. Moreover, targeting HIF-1 using chetomin, disrupter binding its transcriptional co-activator CREB-binding protein (CBP)/p300, abolishes differentiation-inhibitory effect factor-1α. Administration chetomin combination with forskolin significantly suppresses growth an in vivo xenograft model. Analysis 95 tissues revealed increase progressing grade. Taken together, these findings suggest key signal transduction pathway involving contributes defect gliomas sheds new light on therapy factor-1α. Structured digital abstract •  MINT-7292117: CBP (uniprotkb:Q6JHU9) physically interacts (MI:0915) Hif1a (uniprotkb:O35800) anti bait coimmunoprecipitation (MI:0006)