While the relationship between HIF-1 and VEGF in cancer is well-studied, their relative contribution to the angiogenic phenotype in UM has not previously been interrogated.
While HIF1α has been widely studied in cancer, HIF2α offers a potentially more specific and appealing target in glioblastoma given expression in glioma stem cells and not normal neural progenitors, activation in states of chronic hypoxia and expression that correlates with glioma patient survival.
We, therefore, evaluated whether tempol enhances the gene expression via HIF-1α, potentially leading to various applications for cancer gene therapy targeting hypoxic cells.
We suggest a mechanism by which carcinogenic hypoxia modulates the activity of three critical transcription factors (c-MYC, p53, and HIF1), resulting in accumulated ROS and causing hMSCs to undergo cancer-like behavioral changes.
We reviewed the literature by performing an electronic database search via PubMed to identify eligible studies that assessed the impact of LDH5 as a cancer prognostic marker and its association with HIF-1α.
We previously engineered a switchable prodrug-activating enzyme that selectively kills human cancer cells accumulating the cancer marker hypoxia-inducible factor-1α (HIF-1α).
We investigated the roles of HIF-1α and HIF-2α in cancer cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) using human pancreatic cancer cell lines. siRNA-mediated knockdown of HIF-2α, but not HIF-1α, increased susceptibility of two pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL in vitro under normoxic and hypoxic conditions.
We hypothesized that DCA will also reverse the 'pseudohypoxic' mitochondrial signals that lead to HIF1α activation in cancer, even in the absence of hypoxia and inhibit cancer angiogenesis.
We have developed a model system in which HIF1-alpha can be induced within a sub-population of cancer cells, thus enabling us to mimic the effects of heterogeneic HIF1-alpha expression.
We further found that brusatol inhibited c-Myc expression, and showed that overexpression of c-Myc prevented brusatol-induced degradation of HIF-1α and cancer cell death by increasing mitochondrial ROS production and subsequent ROS-mediated transition of ferrous iron to ferric iron.
We found that wogonin decreased the expression of HIF-1α by affecting its stability and reduced the secretion of VEGF, which suppressed angiogenesis in cancer.
We found that the expression of the apoptosis inhibitor ARC (apoptosis repressor with a CARD domain) was induced by hypoxia in a variety of cancer cell types, and its induction is primarily HIF1 dependent.
We created a stable knockdown of HIF-1α and HIF-2α in HepG2 cells and generated cocultures of HepG2 spheroids with embryonic bodies as an in vitro tumor model mimicking the cancer microenvironment.
We also showed that a cell signal factor such as HIF-1α, which might be stabilized under hypoxic environment, is involved in EMT and cancer cell invasive potency.
We additionally present results indicating that MgcRacGAP binding to HIF-1α is specific, since it does not affect the transcriptional activity of HIF-2, a close evolutionary relative of HIF-1 also involved in hypoxia regulation and cancer.
Warburg effect is characterized by the upregulation of HIF-1 and c-Myc regulated LDH-A, even aerobically owing to hypoxic environment and alterations in oncogenes or tumor suppressor genes in cancer.
VHL acts in a ubiquitin ligase complex regulating hypoxia-inducible factor-1 (HIF-1), but the link between this function and cancer development is unclear.
Vascular endothelial growth factor (VEGF) is regulated by the hypoxia-inducible factor 1 (HIF1) pathway and is implicated in tumor progression and patient survival in many types of cancer.