Inhibition of N‐glycosylation by glucosamine hydrochloride inhibits TGF‐β1‐induced LOXL2 secretion

Kamiya, Tetsuro; Kadowaki, Mai; Atobe, Taku; Kunieda, Kana; Morimoto, Koki; Hara, Hirokazu

doi:10.1002/jcb.30404

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…Post-translational modifications are common among LOX enzymes. LOXL2, for instance, has three sites of N-glycosylation (N288, N455, and N644) essential for enzyme secretion [ 18 , 19 ], as well as seventeen disulphide bridges [ 20 ]. A low-resolution structure of the full-length LOXL2 obtained via X-ray scattering and electron microscopy [ 21 ], the crystal structure of a precursor form at a resolution of 2.4 Å [ 22 ] and a 3-D-predicted structure of the C-terminal amine oxidase domain of LOXL2 [ 23 ] are currently available.…”

Section: Introductionmentioning

confidence: 99%

LOXL2 in Cancer: A Two-Decade Perspective

Cano,

Eraso,

Mazón

et al. 2023

IJMS

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Lysyl Oxidase Like 2 (LOXL2) belongs to the lysyl oxidase (LOX) family, which comprises five lysine tyrosylquinone (LTQ)-dependent copper amine oxidases in humans. In 2003, LOXL2 was first identified as a promoter of tumour progression and, over the course of two decades, numerous studies have firmly established its involvement in multiple cancers. Extensive research with large cohorts of human tumour samples has demonstrated that dysregulated LOXL2 expression is strongly associated with poor prognosis in patients. Moreover, investigations have revealed the association of LOXL2 with various targets affecting diverse aspects of tumour progression. Additionally, the discovery of a complex network of signalling factors acting at the transcriptional, post-transcriptional, and post-translational levels has provided insights into the mechanisms underlying the aberrant expression of LOXL2 in tumours. Furthermore, the development of genetically modified mouse models with silenced or overexpressed LOXL2 has enabled in-depth exploration of its in vivo role in various cancer models. Given the significant role of LOXL2 in numerous cancers, extensive efforts are underway to identify specific inhibitors that could potentially improve patient prognosis. In this review, we aim to provide a comprehensive overview of two decades of research on the role of LOXL2 in cancer.

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Section: Introductionmentioning

confidence: 99%

LOXL2 in Cancer: A Two-Decade Perspective

Cano,

Eraso,

Mazón

et al. 2023

IJMS

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A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer

Mezentsev,

Durymanov,

Makarov

2024

Current Oncology

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Invasion and metastasis are important hallmarks of lung cancer, and affect patients’ survival. Early diagnostics of metastatic potential are important for treatment management. Recent findings suggest that the transition to an invasive phenotype causes changes in the expression of 700–800 genes. In this context, the biomarkers restricted to the specific type of cancer, like lung cancer, are often overlooked. Some well-known protein biomarkers correlate with the progression of the disease and the immunogenicity of the tumor. Most of these biomarkers are not exclusive to lung cancer because of their significant role in tumorigenesis. The dysregulation of others does not necessarily indicate cell invasiveness, as they play an active role in cell division. Clinical studies of lung cancer use protein biomarkers to assess the invasiveness of cancer cells for therapeutic purposes. However, there is still a need to discover new biomarkers for lung cancer. In the future, minimally invasive techniques, such as blood or saliva analyses, may be sufficient for this purpose. Many researchers suggest unconventional biomarkers, like circulating nucleic acids, exosomal proteins, and autoantibodies. This review paper aims to discuss the advantages and limitations of protein biomarkers of invasiveness in lung cancer, to assess their prognostic value, and propose novel biomarker candidates.

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The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease

Santiago-Hernandez,

Martin-Lorenzo,

Gómez-Serrano

et al. 2024

IJMS

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Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10–30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients’ follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.

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Inhibition of N‐glycosylation by glucosamine hydrochloride inhibits TGF‐β1‐induced LOXL2 secretion

Cited by 3 publications

References 34 publications

LOXL2 in Cancer: A Two-Decade Perspective

LOXL2 in Cancer: A Two-Decade Perspective

A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer

The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease

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