Certain reports have demonstrated the role of LOX in ECM crosslinking, however, the cancer‑promoting effects of LOX in HCC remain unclear, and whether LOX has a role in the regulation of angiogenesis in HCC TICs has not been elucidated. Lysyl oxidase (LOX) regulates various factors involved in extracellular matrix (ECM) maintenance, migration and angiogenesis. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.Ī highly tumorigenic and malignant sub‑population of HCC containing tumor‑initiating cells (TICs) are defined by high self‑renewal and sphere formation ability. The analyses based on the protein-protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. Similar Kaplan-Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. These findings indicate that lysyl oxidase could be a potential therapeutic target for early recurrence of HCC. High LOX expression is associated with EMT markers and predicts early recurrence and poor survival in patients with HCC.
In vitro, LOX and HIF-1α were involved in migration and invasion capability. Bioinformatic analysis showed that LOX expression was associated with hypoxia-inducible factor-1α (HIF-1α) and the hypoxia cascade, suggesting that HIF-1α or hypoxia regulates LOX expression and induces epithelial-mesenchymal transition (EMT). Multivariate analysis showed that high LOX expression was an independent risk factor for early recurrence (IHC: HR, 2.52 P < .0001).
High LOX expression group had a significantly higher recurrence rate than the low LOX expression group (2-year recurrence rate was 64.0% vs 24.2%, P < .0001 for IHC) and poorer survival rate (5-year rate was 60.1% vs 86.2%, P < .0001 for IHC). Expression of LOX was evaluated by qRT- PCR, and immunohistochemical (IHC) staining. We detected lysyl oxidase (LOX) and validated the clinical significance of LOX in 358 patients who underwent hepatectomy. We searched for genes that would predict HCC recurrence from intrahepatic metastasis in an exhaustive DNA microarray database by searching genes associated with high early recurrence rate and having higher expression in the tumor area compared to background liver. Drug therapy for recurrence of HCC is still limited therefore, identifying new therapeutic targets is urgently needed. Hepatocellular carcinoma (HCC) has high recurrence rates even after curative hepatectomy. The results of this study may provide a new perspective on cervical cancer metastasis and a theoretical basis for clinical treatment.
Compared with SiHa, mono- and co-cultured Conclusion: Co-culture with human umbilical vein endothelial cells promoted the epithelial-to-mesenchymal transition of SiHa cells by activating the NOTCH1/LOX/SNAIL1 pathway in SiHa cells, which enhanced their invasive and metastatic capacities. Methods: Monocultures of SiHa cells, SiHa cells containing a control sequence, and Results: Compared with monocultured SiHa cells, co-cultured SiHa cells showed a significant increase in their invasiveness and expression levels of vimentin, as well as of NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin was significantly reduced and protein activities of MMP-2 and MMP-9 were increased. Background: The aim of this study was to investigate the effect of human umbilical vein endothelial cells on epithelial-to-mesenchymal transition of the cervical cancer cell line SiHa by studying the Notch1/lysyl oxidase (LOX)/SNAIL1 pathway.
0 kommentar(er)
