Furthermore, we demonstrated that PTGIS is a HIF-1α targeted gene, a major regulator in hypoxic cancer progression by activating transcription of various oncogenes.
A negative correlation was determined between miR-548c-3p and hypoxia-inducible factor (HIF) 1α or vascular endothelial growth factor (VEGF) levels, indicating that miR-548c-3p inhibited tumor progression by suppressing the HIF1α-mediated VEGF signaling pathway.
It has been established that HIF-1α is overexpressed in various human cancers, including oral squamous cell carcinoma (OSCC), and orchestrates a wide spectrum of many key cancer molecular pathways involved in diverse tumor progression.
Hence, our findings delineate a molecular pathway that functionally distinguishes HIF-1alpha from HIF-2alpha, and arguing a unique role for HIF-1alpha in tumor progression by promoting genomic instability.
ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-α and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs).
Finally, we found that overexpression of hClock enhanced the expression of angiogenesis-related genes such as HIF-1α, ARNT and VEGF, and promoted epithelial-mesenchymal (-like) transition (EMT) in CRC cells, both of which are considered to be critical for tumor progression.
HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression.
HIF-1 is also activated in cancer cells by tumor suppressor (e.g., VHL) loss of function and oncogene gain of function (leading to PI3K/AKT/mTOR activity) and mediates metabolic alterations that drive cancer progression and resistance to therapy.
Phosphoglycerate kinase 1 (PGK1) is an enzyme of the glycolytic pathway, which is regulated by hypoxia-inducible factor-1α (HIF-1α) and has been described for its role in tumor progression and metastasis in several malignancies.