The roles of HIF-1α and c-Jun in development of resistance to EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) with activating mutation of EGFR have not been explored.
To evaluate the role of VEGF single nucleotide polymorphisms (SNPs), we examined the expression of several angiogenesis-related proteins [VEGF, hypoxia-inducible factor-1α (HIF-1α) and delta-like ligand 4 (Dll4)] and the spread of microvessels in resected non-small cell lung cancer (NSCLC).
We demonstrate that in non-small cell lung cancer (NSCLC), p53 mutants exert a gain-of-function (GOF) effect on HIF-1, thus regulating a selective gene expression signature involved in protumorigenic functions.
The recombinant pcDNA3.0-EGFP plasmids with wild-type or mutant HIF-1α complementary DNA (cDNA) were transfected into H1299 cells, an NSCLC cell line, establishing two H1299 sublines with high expression of HIF-1α.
Our previous studies have demonstrated that HPV-16 oncoproteins enhanced hypoxia-inducible factor-1α (HIF-1α) protein accumulation and vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells, thus contributing to angiogenesis.
The interference of FAM201A impairs its suppression of miR-370, resulting in the upregulation of EGFR and HIF-1α and enhancement of radiosensitivity in NSCLC patients.
Our results showed that CyH significantly inhibited angiogenesis <i>in vitro</i> and <i>in vivo</i>, and suppressed the hemoglobin content and HIF-1α and VEGF protein expression in xenografted NSCLC tissues of nude mice.
HIF1α genetic variants and protein expressions determine the response to platinum based chemotherapy and clinical outcome in patients with advanced NSCLC.
The correlation between HIF-1α and EMT-related transcription factors in NSCLC tissues was analyzed by immunohistochemical staining and Spearman rank correlation coefficient.
While HIF-1 expression did not correlate with poor survival in the NSCLC validation cohort (N = 442), established targets of hypoxia signaling (PLAUR, ADM, CA9) were significantly associated with poor overall survival.
Finally, HIF2α, but not HIF1α, was required for ALCL growth in vivo whereas the growth and metastasis potential of ALK-rearranged NSCLC required both HIF1α and HIF2α.
To investigate the consequences of inhibiting HIF activity in lung cancers, we deleted Hif-1alpha or Hif-2alpha in an established Kras(G12D)-driven murine NSCLC model.
This study showed that the SLCO1B3 c.699 G>A polymorphism may predict anemia and ABCB1, HIF1A polymorphism are highly predictive for worse survival in advanced NSCLC with first-line paclitaxel and carboplatin.
These results suggest that low dose erlotinib-cisplatin combination exhibits its anti-tumor activity by targeting angiogenesis through the modulation of the c-MYC/HIF-1α/VEGF pathway in NSCLC with EGFR exon 19 deletions.
These results show that circPIP5K1A acted as a tumor promoter through a novel circPIP5K1A/miR-600/HIF-1α axis, which provides candidate markers and therapeutic targets for NSCLC.
Specific HIF-1alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number , which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number , which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13.
The results demonstrated that the prognostic significance of HIF-1α should be validated in the context of EGFR status in NSCLC patients, and the gene and protein status of EGFR and HIF-1α will be important to help select patients most likely to derive the greatest clinical benefit from EGFR or HIF-1α targeted therapies.
In the present study, the effects of hypoxia on the response of the NSCLC A549 cell line to the clinically relevant cytotoxic cisplatin were evaluated via regulating hypoxia inducible facor-1α (HIF-1α) and p53.