Retraction Note: Lysyl oxidase is essential for hypoxia-induced metastasis

Erler, Janine T.; Bennewith, Kevin L.; Nicolau, Monica; Dornhöfer, Nadja; Kong, Christina S.; Le, Quynh‐Thu; Ashley, Jen-Tsan; Jeffrey, Stefanie S.; Giaccia, Amato J.

doi:10.1038/s41586-020-2112-4

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[74] Although the increased activity of LOX under oxygen deprivation has been known for a long time, [75] it was only pointed out in connection with cancer development in 2006 in a highly regarded paper, [76] which, however, recently had to be withdrawn due to improper processing of Western blot images. [77] Nevertheless, the conclusions drawn from this work stand, as they have been confirmed by subsequent work, including that of other groups. [74,78] Similarly, expression of the lysyl oxidase isozymes LOXL2 [79] and LOXL4 [80] is under transcriptional control of HIF-1.…”

Section: Action On Extracellular Substratessupporting

confidence: 75%

“…Since the LOX gene has a hypoxia‐responsive element in its promoter, this also results in the upregulation of LOX expression [74] . Although the increased activity of LOX under oxygen deprivation has been known for a long time, [75] it was only pointed out in connection with cancer development in 2006 in a highly regarded paper, [76] which, however, recently had to be withdrawn due to improper processing of Western blot images [77] . Nevertheless, the conclusions drawn from this work stand, as they have been confirmed by subsequent work, including that of other groups [74,78] .…”

Section: Functions Of Lysyl Oxidases In Tumour Progression and Metast...mentioning

confidence: 99%

See 1 more Smart Citation

Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

et al. 2023

View full text Add to dashboard Cite

The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as drivers of fibrotic diseases. These insights have considerably stimulated drug discovery efforts towards lysyl oxidases as targets over the last decade. This review article summarises the biochemical and structural properties of theses enzymes. Their involvement in tumour progression and metastasis is highlighted from a biochemical point of view, taking into consideration both the extracellular and intracellular action of lysyl oxidases. More recently reported inhibitor compounds are discussed with an emphasis on their discovery, structure‐activity relationships and the results of their biological characterisation. Molecular probes developed for imaging of lysyl oxidase activity are reviewed from the perspective of their detection principles, performance and biomedical applications.

show abstract

Section: Action On Extracellular Substratessupporting

confidence: 75%

Section: Functions Of Lysyl Oxidases In Tumour Progression and Metast...mentioning

confidence: 99%

Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Collagen I (Col-I), collagen III (Col-III), and ELN in hDFs are the main components of the vascular extracellular matrix, and under 2% O 2 , the expression of their respective mRNA ( COL 1 A 1, COL 3 A 1, and ELN ) increased more significantly than that at the normal O 2 concentration (Figure A–C). , Fibronectin (FN) and fibrillin-1 (FBN1) are components of the ECM that promote the assembly of proelastin into ELN, and the increase in the expression of their respective mRNA ( FN 1 and FBN 1) was associated with accelerated generation of ECM in 2 days (Figure D,E). Lysyl oxidase (LOX) plays a positive role in the cross-linking of collagen and ELN and the maintenance of ECM function, , and the expression of LOXL mRNA under hypoxia increased significantly compared with that under normoxia (Figure F). LH-2 is a lysine hydroxylase that directly enhances the stability of collagen and prevents the degradation of collagen caused by the instability of the cross-linking structure of other collagen fibers .…”

Section: Resultsmentioning

confidence: 99%

Construction of Rapid Extracellular Matrix-Deposited Small-Diameter Vascular Grafts Induced by Hypoxia in a Bioreactor

Guo

Huang

Lei

et al. 2023

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

Cardiovascular disease has become one of the most globally prevalent diseases, and autologous or vascular graft transplantation has been the main treatment for the end stage of the disease. However, there are no commercialized small-diameter vascular graft (SDVG) products available. The design of SDVGs is promising in the future, and SDVG preparation using an in vitro bioreactor is a favorable method, but it faces the problem of long-term culture of >8 weeks. Herein, we used different oxygen (O2) concentrations and mechanical stimulation to induce greater secretion of extracellular matrix (ECM) from cells in vitro to rapidly prepare SDVGs. Culturing with 2% O2 significantly increased the production of the ECM components and growth factors of human dermal fibroblasts (hDFs). To accelerate the formation of ECM, hDFs were seeded on a polycaprolactone (PCL) scaffold and cultured in a flow culture bioreactor with 2% O2 for only 3 weeks. After orthotopic transplantation in rat abdominal aorta, the cultured SDVGs (PCL–decellularized ECM) showed excellent endothelialization and smooth muscle regeneration. The vascular grafts cultured with hypoxia and mechanical stimulation could accelerate the reconstruction speed and obtain an improved therapeutic effect and thereby provide a new research direction for improving the production and supply of SDVGs.

show abstract

“…Meanwhile, it has been demonstrated that LOX was also essential for stimulating endothelial cells and angiogenesis. However, LOX itself was not responsible for promoting angiogenesis but indirectly promoted angiogenesis by upregulating of VEGF [ 30 ]. In this study, we concluded that LOX might play important parts in angiogenesis triggered by hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Exploration of Hub Genes and Potential Therapeutic Drugs for Endothelial Dysfunction in Hypoxic Pulmonary Hypertension

Chen

Lin

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Hypoxic pulmonary hypertension (HPH) is a fatal chronic pulmonary circulatory disease, characterized by hypoxic pulmonary vascular constriction and remodeling. Studies performed to date have confirmed that endothelial dysfunction plays crucial roles in HPH, while the underlying mechanisms have not been fully revealed. The microarray dataset GSE11341 was downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between hypoxic and normoxic microvascular endothelial cell, followed by Gene Ontology (GO) annotation/Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis, and protein-protein interaction (PPI) network construction. Next, GSE160255 and RT-qPCR were used to validate hub genes. Meanwhile, GO/KEGG and GSEA were performed for each hub gene to uncover the potential mechanism. A nomogram based on hub genes was established. Furthermore, mRNA-miRNA network was predicted by miRNet, and the Connectivity Map (CMAP) database was in use to identify similarly acting therapeutic candidates. A total of 148 DEGs were screened in GSE11341, and three hub genes (VEGFA, CDC25A, and LOX) were determined and validated via GSE160255 and RT-qPCR. Abnormalities in the pathway of vascular smooth muscle contraction, lysosome, and glycolysis might play important roles in HPH pathogenesis. The hub gene-miRNA network showed that hsa-mir-24-3p, hsa-mir-124-3p, hsa-mir-195-5p, hsa-mir-146a-5p, hsa-mir-155-5p, and hsa-mir-23b-3p were associated with HPH. And on the basis of the identified hub genes, a practical nomogram is developed. To repurpose known and therapeutic drugs, three candidate compounds (procaterol, avanafil, and lestaurtinib) with a high level of confidence were obtained from the CMAP database. Taken together, the identification of these three hub genes, enrichment pathways, and potential therapeutic drugs might have important clinical implications for HPH diagnosis and treatment.

show abstract

Retraction Note: Lysyl oxidase is essential for hypoxia-induced metastasis

Cited by 4 publications

References 0 publications

Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

Construction of Rapid Extracellular Matrix-Deposited Small-Diameter Vascular Grafts Induced by Hypoxia in a Bioreactor

Bioinformatic Exploration of Hub Genes and Potential Therapeutic Drugs for Endothelial Dysfunction in Hypoxic Pulmonary Hypertension

Contact Info

Product

Resources

About