CRC with pNF-κB expression had significantly higher SIRT1 expression levels and hypoxia-inducible factor-1α expression levels than CRC without pNF-κB expression (P < 0.001 and P < 0.001, respectively).
Hypoxia inducible factor-1α (HIF-1α) is a major regulator of tumorigenesis in hypoxic conditions and therefore represents a potential therapeutic target in colorectal cancer (CRC).
Abnormally expressed glucose transporters (GLUTs) are colocalized with hypoxia (Hx) inducible factor (HIF)1α in peri-necrotic regions in human colorectal carcinoma.
Among these identified TFs, we obtained a novel six-node module consisting of ATF2-P53-JNK1-ELK1-EPHB2-HIF1A, from which the novel JNK1-ELK1 association could potentially be a significant marker for CRC.
Collectively, we demonstrated that KLF2 mediates CRC cell biological processes including cell growth and apoptosis via regulating the HIF-1α/Notch-1 signal pathway.
Consistent with this pro-tumorigenic function for NQO1, high NQO1 expression levels correlate with increased HIF-1α expression and poor colorectal cancer patient survival.
Despite the careful selection of the tumor samples, our findings do not appear to confirm, for colorectal cancers, the significant association between HIF-1alpha overexpression and tumor aggressiveness or unfavorable prognosis demonstrated for cancers of other sites.
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.
Finally, the knockdown of galectin-1 by its specific shRNA can significantly reduce hypoxia-induced invasion and migration of CRC cell line, and the ectopic expression of galectin-1 can remarkably restore invasion and migration abilities of HIF-1alpha-knocked SW620 cells, proposing that galectin-1 mediates the HIF-1-induced migration and invasion of CRC cells during hypoxia.
Finally, we examined the relationship among mutated KRAS, hypoxia-inducible factor 1α (HIF-1α), and maximum standardized uptake value with 51 clinical CRC samples.
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.
Furthermore, HIF-1alpha expression observed in 10 of the 16 (62.5%) poorly differentiated CRCs showed a topological correlation with loss of CDX2 expression.
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).
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.
Here, we identified a hypoxia-triggered feedback loop that involves hypoxia-inducible transcription factor 1α (HIF-1α)-mediated repression of miR-338-5p and confers drug resistance in CRC.