HIF-1α is predominantly involved in the early stages of cancer, whereas HIF-2α is actively involved in the later stages; in addition, chronic (prolonged) rather than acute (short) hypoxia is a feature of metastasis and chemoresistance that occur during the later stages of cancer.
Hypoxia inducible factor-1α (HIF-1α), another cancer stem cell marker, was found in the nucleus of the former, but found in the cytoplasm of the cells in a monolayer.
Hypoxia‑inducible‑factor 1α (HIF‑1α) is a marker for poor prognosis in the majority of the cancer types, and it has been revealed to be essential for maintaining cancer stem cells (CSCs).
HIF-1 is regarded as a promising target for the drugs used in cancer chemotherapy, and creating readily accessible templates for the development of synthetic drug candidates that could inhibit HIF-1 transcriptional activity is an important pursuit.
K477RHIF-1α mutation and specific cancer-associated Parkin mutations largely abolish the functions of Parkin to ubiquitinate HIF-1α and inhibit cancer metastasis.
A mechanistic study further indicated that the protein expression but not mRNA transcription of HIF‑1α, a well‑known transcription factor critical for dysregulated cancer cell glucose metabolism, was dramatically inhibited in berberine‑treated colon cancer cell lines.
A statistically significant association between the HIF-1α GA/AA genotype and cancer risk was found in the meta-analysis (OR, 1.79; 95% CI, 1.12-2.86; P(heterogeneity) < 0.00001).
A subset of relevant clinically observed mutations to pVHL are thought to cause weaker binding of HIF-1α and are associated with cancer and cardiovascular diseases.
Accordingly, HIF-1α, involved in cell cycle deregulation, apoptosis, angiogenesis induction and proliferation in cancer, constitutes a predictive marker of resistance to radiotherapy (RT).
Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions.
Activity of HIF-1α in cancer cells is regulated at the transcriptional, translational and posttranslational level by multiple inter- and coacting molecular pathways.
After an appropriate number of cancer tissues were taken, the experimental group was treated with oral administration of 500 mg vitamin B3 every day, while the placebo group was treated with oral administration of the same amount of placebo; after 1 week, the skin cancer tissues in the same part were taken, and the skin tissues of healthy people were taken as the control group; the mRNA and protein expression levels of HIF-1α and p53 in tissues were detected.
Although many of the HIF inhibitors reviewed in this patent survey possess inhibitory activity against cancer and HIF-related diseases, the compounds are still in the early stages of development, most likely due to the complexity of the HIF-1 pathway and their different mechanisms of action for HIF inhibition.
Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases.
An understanding of underlying mechanisms involved in the activation of HIF-1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer.
Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown.