We show that a high LOX expression in primary tumors from patients with colorectal cancer was associated with poor clinical outcome, irrespective of HIF-1 In addition, LOX was expressed by tumor cells in the bone marrow from colorectal cancer patients with bone metastases.
Finally, knockdown of hypoxia inducible factor (HIF-1α) by shRNA reversed the role of Smad7, CXCR-4, PDGF-A, TGF-A and ANGPTL-4 overexpression in HCT-116 cells, these findings provide the potential angiogenic targets for the treatment of colorectal cancer.
Here, we found that hypoxia inducible factor-1α (HIF-1α) mRNA levels were positively correlated with Ascl2 mRNA levels and inversely correlated with miR-200b in CRC samples.
In the present study, we investigated the molecular mechanisms underlying brusatol-induced HIF-1α degradation and cell death in colorectal cancer under hypoxia (0.5% O<sub>2</sub>).
Collectively, we demonstrated that KLF2 mediates CRC cell biological processes including cell growth and apoptosis via regulating the HIF-1α/Notch-1 signal pathway.
We show that re-expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional activity of HIF1α and reduced the expression and secretion of VEGF in both normoxic and hypoxic conditions.
In a CRC cell line and human CRC tissue exposed to hypoxia, induced heat-shock 70-kDa protein-1-like (HSPA1L) expression stabilized hypoxia-inducible factor-1α (HIF-1α) protein and promoted PrP<sup>C</sup> accumulation and tumorigenicity in vivo.
Here we aimed to further elucidate HIF-1α protein expression in serrated and non-serrated colorectal carcinomas (CRCs) and their precursor lesions and its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD).
Consistent with this pro-tumorigenic function for NQO1, high NQO1 expression levels correlate with increased HIF-1α expression and poor colorectal cancer patient survival.
Our study reveals a regulatory role for HIF-1α in VM and suggests that targeting either HIF-1α or EMT may be a valuable strategy for the elimination of CRC metastasis.
For proof-of-concept, we targeted the oncogenic KRAS and HIF pathways, since oncogenic KRAS has been shown to be required for cancer initiation and progression, and HIF-1α and HIF-2α are induced by the majority of mutated oncogenes and tumor suppressor genes in CRC.
This article reviews the central role of HIF1α in CRC angiogenesis, metastasis, and progression as well as the strategies to target HIF1α stabilization.
These findings highlight the critical role of FIH-1 in CRC and indicate FIH-1 functions as a tumor suppressor in human CRC by repressing HIF1α pathway.
The detection for the mechanisms of miR-199a on the development of CRC showed that the anticarcinogenic effect of miR-199a might be produced through HIF-1α/VEGF pathway.