Hypoxia-inducible factor–1 and associated upstream and downstream proteins in the pathophysiology and management of glioblastoma

Abstract

<jats:p>Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an exceptionally poor patient outcome despite aggressive therapy including surgery, radiation, and chemotherapy. This aggressive phenotype may be associated with intratumoral hypoxia, which probably plays a key role in GBM tumor growth, development, and angiogenesis. A key regulator of cellular response to hypoxia is the protein hypoxia-inducible factor–1 (HIF-1). An examination of upstream hypoxic and nonhypoxic regulation of HIF-1 as well as a review of the downstream HIF-1–regulated proteins may provide further insight into the role of this transcription factor in GBM pathophysiology. Recent insights into upstream regulators that intimately interact with HIF-1 could provide potential therapeutic targets for treatment of this tumor. The same is potentially true for HIF-1–mediated pathways of glycolysis-, angiogenesis-, and invasion-promoting proteins. Thus, an understanding of the relationship between HIF-1, its upstream protein regulators, and its downstream transcribed genes in GBM pathogenesis could provide future treatment options for the care of patients with these tumors.</jats:p>

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

“…The survival time for each rat after inoculation was measured. response to the degree of hypoxia in tumor microenvironment (Womeldorff et al, 2014;Courtnay et al, 2015), we determined HIF-1α in tumor tissues using immunohistochemistry and Western blot. As expected, HIF-1α expression was reduced in C6 tumors in response to the DA treatment as compared with the control (Figs.…”

Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis

“…Hypoxia is an important feature of glioma microenvironment leading to intratumoral necrosis and angiogenesis [3].…”

“…Hypoxia is implicated in promoting glioma aggressiveness, chemoresistance and antiangiogenic therapy [3]. Glioblastoma has strong activity of migration and invasion [2], which is associated to low oxygen condition of tumor microenvironment [4][5][6].…”

“…Gliomas show high morbidity and mortality due to their strong aggressiveness. This aggressive phenotype is possibly relevant to hypoxia, which is one of the most remarkably characteristics of glioma microenvironment and might play a crucial role in glioma growth, development, and angiogenesis [3]. It has been documented that hypoxia also induces migration and invasion of glioma cells [4][5][6], which involves a series of transduction pathways and signal molecules.…”

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

“…brain, high resistance to apoptosis [4], robust angiogenesis [5], tumor cell heterogeneity [6], proliferation of cancer stem-like cells [7], and an inflammatory state that results in recruitment of circulating lymphocytes and monocytes. GBM tumors consist of a heterogeneous population of tumor cells and contain immune cells that, with tumor vasculature and the extracellular matrix, constitute the tumor microenvironment.…”