Lysyl oxidase family members in urological tumorigenesis and fibrosis

Li, Tao; Wu, Changjing; Gao, Liang; Qin, Feng; Wang, Qiang; Yuan, Jiuhong

doi:10.18632/oncotarget.24948

Cited by 25 publications

(23 citation statements)

References 62 publications

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“…It is particularly important to fill these knowledge gaps, as LOX has been shown to be a promising target for therapeutic intervention in cancer [ 3 , 78 , 79 ] and in vascular [ 80 ], myocardial [ 81 , 82 ], peritoneal [ 83 ] liver [ 84 ] and urological disorders [ 85 ], in adipose tissue dysfunction with an inflammatory component [ 86 ] and in inflammation in Crohns’ disease [ 87 ]. In some of these conditions, fibrosis is the pathological endpoint linking aberrant LOX to its ECM cross-linking activity as an attractive target for LOX-inhibitory therapies.…”

Section: Discussionmentioning

confidence: 99%

Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways

Laczkó

Csiszár

2020

Biomolecules

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Cu-dependent lysyl oxidase (LOX) plays a catalytic activity-related, primary role in the assembly of the extracellular matrix (ECM), a dynamic structural and regulatory framework which is essential for cell fate, differentiation and communication during development, tissue maintenance and repair. LOX, additionally, plays both activity-dependent and independent extracellular, intracellular and nuclear roles that fulfill significant functions in normal tissues, and contribute to vascular, cardiac, pulmonary, dermal, placenta, diaphragm, kidney and pelvic floor disorders. LOX activities have also been recognized in glioblastoma, diabetic neovascularization, osteogenic differentiation, bone matrix formation, ligament remodeling, polycystic ovary syndrome, fetal membrane rupture and tumor progression and metastasis. In an inflammatory context, LOX plays a role in diminishing pluripotent mesenchymal cell pools which are relevant to the pathology of diabetes, osteoporosis and rheumatoid arthritis. Most of these conditions involve mechanisms with complex cell and tissue type-specific interactions of LOX with signaling pathways, not only as a regulatory target, but also as an active player, including LOX-mediated alterations of cell surface receptor functions and mutual regulatory activities within signaling loops. In this review, we aim to provide insight into the diverse ways in which LOX participates in signaling events, and explore the mechanistic details and functional significance of the regulatory and cross-regulatory interactions of LOX with the EGFR, PDGF, VEGF, TGF-β, mechano-transduction, inflammatory and steroid signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways

Laczkó

Csiszár

2020

Biomolecules

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“…Such a difference in activities is also documented by recent publications. The involvement of one or more members of LOXs (in the active form or as the pro-peptide) was evaluated in different cancers and conditions: experimental ornithine decarboxylase-and RAS-transformed mouse fibroblasts and human melanoma cells, renal and bladder, and gastric cancers, respectively [91][92][93]. LOXs showed variability of expression during tumor development, with the possibility of exerting either promotion or even inhibition effects depending on the type of LOX expressed, the tumor type, and the microenvironment.…”

Section: Final Remarks and Conclusionmentioning

confidence: 99%

Lysyl oxidases: linking structures and immunity in the tumor microenvironment

Tenti

Vannucci

2019

Cancer Immunol Immunother

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The lysyl oxidases (LOXs) are a family of enzymes deputed to cross-link collagen and elastin, shaping the structure and strength of the extracellular matrix (ECM). However, many novel "non-canonical" functions, alternative substrates, and regulatory mechanisms have been described and are being continuously elucidated. The activity of LOXs, therefore, appears to be integrated into a complex network of signals regulating many cell functions, including survival/proliferation/differentiation. Among these signaling pathways, TGF-β and PI3K/Akt/mTOR, in particular, cross-talk extensively with each other and with LOXs also initiating complex feedback loops which modulate the activity of LOXs and direct the remodeling of the ECM. A growing body of evidence indicates that LOXs are not only important in the homeostasis of the normal structure of the ECM, but are also implicated in the establishment and maturation of the tumor microenvironment. LOXs' association with advanced and metastatic cancer is well established; however, there is enough evidence to support a significant role of LOXs in the transformation of normal epithelial cells, in the accelerated tumor development and the induction of invasion of the premalignant epithelium. A better understanding of LOXs and their interactions with the different elements of the tumor immune microenvironment will prove invaluable in the design of novel anti-tumor strategies.

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“…[35][36][37] The differential expression of the LOX family or dysregulated oxidase activity may play important roles in the pathogenesis of multiple diseases, including both solid and liquid tumors. [35][36][37] The differential expression of the LOX family or dysregulated oxidase activity may play important roles in the pathogenesis of multiple diseases, including both solid and liquid tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Lysyl oxidase and its family members LOXL 1 to 4 are copper-containing amine oxidases that catalyze the covalent cross-linkages of collagen and/or elastin in the extracellular matrix. [35][36][37] The differential expression of the LOX family or dysregulated oxidase activity may play important roles in the pathogenesis of multiple diseases, including both solid and liquid tumors. 38 Among the LOX family members, LOXL2 has been considered to be a critical regulatory factor in tumor initiation and progression.…”

Section: Discussionmentioning

confidence: 99%

A novel splice variant of LOXL2 promotes progression of human papillomavirus–negative head and neck squamous cell carcinoma

Liu

Guo

Sakai

et al. 2019

Cancer

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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently diagnosed cancers worldwide. LOXlike (LOXL) 2 (LOXL2) demonstrates alternative splicing events in patients with human papillomavirus (HPV)-negative HNSCC. The current study explored the role of a dominant LOXL2 variant in HPV-negative HNSCC. METHODS: Expression of the LOXL2 variant was analyzed using The Cancer Genome Atlas cohorts and validated using quantitative reverse transcriptase-polymerase chain reaction in a separate primary tumor set. The authors defined the effect of LOXL2 splice variants in assays for cell proliferation using a cell viability assay and colony formation assay. Cell migration and invasion were examined using a cell scratch assay and transwell cell migration and invasion assay in LOXL2 splice variant gain and loss of expression cells. Western blot analysis and gene set enrichment analysis were used to explore the potential mechanism of the LOXL2 splice variant in HPV-negative HNSCC. RESULTS: Expression of a novel LOXL2 variant was found to be upregulated in The Cancer Genome Atlas HPV-negative HNSCC, and confirmed in the separate primary tumor validation set. Analyses of loss and gain of function demonstrated that this LOXL2 variant enhanced proliferation, migration, and invasion in HPV-negative HNSCC cells and activated the FAK/AKT pathway. A total of 837 upregulated and 820 downregulated genes and 526 upregulated and 124 downregulated pathways associated with LOXL2 variant expression were identified using gene set enrichment analysis, which helped in developing a better understanding of the networks activated by this LOXL2 variant in patients with HPV-negative HNSCC. CONCLUSIONS: The novel LOXL2 variant can promote the progression of HPV-negative HNSCC, in part through FAK/AKT pathway activation, which may provide a new potential therapeutic target among patients with HPV-negative HNSCC. Cancer 2020;126:737-748.

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Lysyl oxidase family members in urological tumorigenesis and fibrosis

Cited by 25 publications

References 62 publications

Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways

Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways

Lysyl oxidases: linking structures and immunity in the tumor microenvironment

A novel splice variant of LOXL2 promotes progression of human papillomavirus–negative head and neck squamous cell carcinoma

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