HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway

Qiang, Lei; Wu, Tong; Hw, Zhang; Lü, Ning; R, Hu; Yj, Wang; Zhao, Lu; Fh, Chen; Xt, Wang; Qd, You; Ql, Guo

doi:10.1038/cdd.2011.95

Cited by 268 publications

(213 citation statements)

References 42 publications

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“…The work by Conley et al (1) provided evidence that antiangiogenic agents increase cancer stem cells through the generation of tumor hypoxia. These findings are in accordance with the findings showing that hypoxia induces stem cell markers expression in cancer cells (2,3) and that antiangiogenic therapy elicits malignant progression of tumors (4). Thus, there is now sufficient evidence to reconsider the role of tumor angiogenesis in cancer progression.…”

supporting

confidence: 82%

Angiogenesis and the tumor space–time continuum

Nugue¹,

Wion

2012

Proc. Natl. Acad. Sci. U.S.A.

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Tumors invade space through cancer cell proliferation and tumor mass expansion. Tumor growth is maintained over time using the cancer stem cell pool, which is the cell population with self-renewal potential. The work by Conley et al.(1) provided evidence that antiangiogenic agents increase cancer stem cells through the generation of tumor hypoxia. These findings are in accordance with the findings showing that hypoxia induces stem cell markers expression in cancer cells (2, 3) and that antiangiogenic therapy elicits malignant progression of tumors (4). Thus, there is now sufficient evidence to reconsider the role of tumor angiogenesis in cancer progression. Tissues need nutrients and oxygen for growth, and tumors behave as other tissues. This view is the classical view, in which, according to the work by Folkman (5), the role of tumor angiogenesis fulfills the function of normal vessels that is to deliver oxygen and metabolites and remove waste products. However, tumor vessels are abnormal and fail to fulfill these functions. Therefore, tumors have naturally chronic and cyclic hypoxic regions. This paradoxical consequence of tumor angiogenesis is that, because of its deficiencies, it also generates hypoxia. In pathology such as cancer, a defect in a physiological process does not necessarily suppress the function of the process but can generate a novel function required for disease development. Here, the other function of tumor angiogenesis is to maintain tumor growth over time through cancer stem cell increase. This dual nature of tumor angiogenesis ensures a balance between growth over space (by providing oxygen and nutrients; i.e., physiological function) and growth over time (by generating hypoxic regions that increase the cancer stem cell pool; i.e., pathophysiological function). Hence, tumors require both the physiological and pathophysiological functions of tumor angiogenesis. Therefore, the significance of tumor angiogenesis is the generation of a tumor space-time continuum.

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supporting

confidence: 82%

Angiogenesis and the tumor space–time continuum

Nugue¹,

Wion

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…HIF-1α is able to regulate the transcription of various hypoxia-sensitive factor genes (28). Studies have indicated that the 401 to 603 amino acid residues of HIF-1α have an oxygen-dependent degradation domain (29,30).…”

Section: Discussionmentioning

confidence: 99%

Expression and role of microRNA 18b and hypoxia inducible factor‑1α in placental tissues of preeclampsia patients

Wang

Weng

et al. 2017

Exp Ther Med

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Abstract. Abnormal expression of hypoxia inducible factor-1α (HIF-1α) is closely associated with various diseases. By detecting the mRNA and protein expression levels of microRNA 18b (miR-18b) and HIF-1α in placental tissues of preeclampsia (PE) patients and studying the effects of miR-18b on total cellular metabolic activity, migration and invasion in normal human trophoblast cell lines (HTR-8/SVneo), the present study aimed to investigate the effect of miR-18b on targeted regulation of HIF-1α and its clinical significance in the development of PE. Expression levels of miR-18b and HIF-1α mRNA in PE placental tissues were detected by reverse transcription-quantitative polymerase chain reaction and corresponding expression levels of HIF-1α protein were analyzed by western blotting. miR-18b overexpression and inhibited miR-18b expression in HTR-8/SVneo cells, which were constructed by transfecting miR-18b mimic and inhibitor, respectively, were investigated and the total cellular metabolic activity, migration and invasion abilities in different groups of cells were compared. Expression levels of miR-18b were significantly reduced in PE placental tissues and miR-18b inhibitor-transfected HTR-8/SVneo cells, whereas the expression levels of HIF-1α were significantly increased in PE placental tissues and significantly decreased in miR-18b mimic-transfected HTR-8/SVneo cells. Overexpression of miR-18b inhibited the expression of HIF-1α and reduced the cell invasion, migration and viability of HTR-8/SVneo cells. However, inhibition of miR-18b expression promoted the expression of HIF-1α and increased the cell invasion, migration and total cellular metabolic activity of HTR-8/SVneo cells. The present study indicated that abnormal expression of HIF-1α exhibited in PE placental tissues was regulated by miR-18b. Furthermore miR-18b expression was demonstrated to affect cell invasion, migration and viability through target regulation of HIF-1α. The results of the present study suggest that miR-18b and HIF-1α may have important roles in the development of PE.

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“…[75][76][77] HIF-1 is required to promote interactions with NICD and potentiate the stabilization of the CSL-NICD complex under hypoxia conditions, while induction of Hes1 protects progenitor cells, as well as tumor stem cells, against differentiation. [78][79][80][81] Non-canonical Notch signaling pathway Notch signaling pathway can exert its biological function independently of its ligands, receptors or CSL in vertebrates. Early evidence for non-canonical Notch has been implicated in normal tissue as well as tumor.…”

Section: Canonical Notch Signaling Pathwaymentioning

confidence: 99%