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Lysyl Oxidase Family Proteins: Prospective Therapeutic Targets in Cancer.

ABSTRACT: The lysyl oxidase (LOX) family, consisting of LOX and LOX-like proteins 1-4 (LOXL1-4), is responsible for the covalent crosslinking of collagen and elastin, thus maintaining the stability of the extracellular matrix (ECM) and functioning in maintaining connective tissue function, embryonic development, and wound healing. Recent studies have found the aberrant expression or activity of the LOX family occurs in various types of cancer. It has been proved that the LOX family mainly performs tumor microenvironment (TME) remodeling function and is extensively involved in tumor invasion and metastasis, immunomodulation, proliferation, apoptosis, etc. With relevant translational research in progress, the LOX family is expected to be an effective target for tumor therapy. Here, we review the research progress of the LOX family in tumor progression and therapy to provide novel insights for future exploration of relevant tumor mechanism and new therapeutic targets.

SUBMITTER: Wang W

PROVIDER: S-EPMC9602794 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Lysyl Oxidase Family Proteins: Prospective Therapeutic Targets in Cancer.

Wang Wei W Wang Xiangjun X Yao Feng F Huang Chao C

International journal of molecular sciences 20221014 20

The lysyl oxidase (LOX) family, consisting of LOX and LOX-like proteins 1-4 (LOXL1-4), is responsible for the covalent crosslinking of collagen and elastin, thus maintaining the stability of the extracellular matrix (ECM) and functioning in maintaining connective tissue function, embryonic development, and wound healing. Recent studies have found the aberrant expression or activity of the LOX family occurs in various types of cancer. It has been proved that the LOX family mainly performs tumor m ...[more]

PMID: 36293126

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Project description:IntroductionLysyl oxidase (LOX; ExPASy ENZYME entry: EC 1.4.3.13) and members of the LOX-like family, LOXL1-LOXL4, are copper-dependent enzymes that can modify proteins of the extracellular matrix. Expression of LOX is elevated in many human cancers, including breast cancer. LOX expression correlates with the level of tissue hypoxia, and it is known to play a critical role in breast cancer metastasis. The goal of the present study was to target LOX with (1) molecular probe fluorescent labeling to visualize LOX in vitro and (2) a radiolabeled peptide to target LOX in vivo in three different preclinical models of breast cancer.MethodsGene expression of all five members of the LOX family was analyzed at the transcript level via microarray analysis using tissue biopsy samples from 176 patients with breast cancer. An oligopeptide sequence (GGGDPKGGGGG) was selected as a substrate-based, LOX-targeting structure. The peptide was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy experiments with the murine breast cancer cell line EMT-6. In vivo molecular imaging experiments were performed using a C-terminal amidated peptide, GGGDPKGGGGG, labeled with a short-lived positron emitter, fluorine-18 ((18)F), for positron emission tomography (PET) in three different breast cancer models: EMT6, MCF-7 and MDA-MB-231. The PET experiments were carried out in the presence or absence of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX.ResultsImmunostaining experiments using a LOX-specific antibody on EMT-6 cells cultured under hypoxic conditions confirmed the elevation of LOX expression in these cells. An FITC-labeled oligopeptide, FITC-Ava-GGGDPKGGGGG-NH2, was found to be localized in different cellular compartments under these conditions. After injection of [(18)F]fluorobenzoate-GGGDPKGGGGG-NH2, radioactivity uptake was visible in all three breast cancer models in vivo. Tumor uptake was reduced by predosing the animals with 2 mg of BAPN 4 h or 24 h before injection of the radiotracer.ConclusionsThe present data support further investigation into the development of LOX-binding radiolabeled peptides as molecular probes for molecular imaging of LOX expression in cancer.

Dataset Information

Lysyl Oxidase Family Proteins: Prospective Therapeutic Targets in Cancer.

Publications

Lysyl Oxidase Family Proteins: Prospective Therapeutic Targets in Cancer.

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