TNF-α increases cardiac fibroblast lysyl oxidase expression through TGF-β and PI3Kinase signaling pathways

Voloshenyuk, Tetyana G; Hart, Andrew; Khoutorova, Elena; Gardner, Jason D.

doi:10.1016/j.bbrc.2011.08.109

Cited by 74 publications

(59 citation statements)

References 31 publications

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“…Overexpression of TGFβ correlates with a poor prognosis for gastric cancer [38,39], especially the diffuse-type gastric cancer [40]. In addition, several studies suggest that TGFβ can induce the expression of the LOX family [41,42]. Therefore, we analyzed the effect of TGFβ1 on LOX family members in diffuse-type gastric cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…TGFβ1 increased the expression levels of LOXL3 and LOXL4 in OCUM-2MLN and OCUM-2MD3 cells, but not in OCUM-2M cells. It has been reported that TGFβ signaling regulates the expression of LOX members [41][42][43]. TGFβ also regulates tumor activities, creating reactive stroma and metastasis [14,44]; LOXL3 and LOXL4 may thus be candidates downstream to TGFβ signaling in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

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Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Kasashima¹,

Yashiro²,

Okuno³

et al. 2018

Digestion

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Background/Aims: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. Methods: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members – LOXL1, LOXL3, and LOXL4 – were investigated by immunohistochemical studies. The effect of the transforming growth factor β1 (TGFβ1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. Results: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFβ decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. Conclusion: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Kasashima¹,

Yashiro²,

Okuno³

et al. 2018

Digestion

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“…Thus, any alteration of LOXL1 activation may lead to the abnormal aggregation of elastic fiber components into XFS fibrils. Moreover, lysyl oxidase family members have been shown to be up-regulated by transforming growth factor b1 (TGF-b1) 111 and oxidative stress 112 and may therefore act as co-modulating external factors in XFS pathophysiology. It may be hypothesized that the abnormal matrix process characteristic of XFS could be activated by oxidative stress and TGF-b1 in the background of the high-risk LOXL1 haplotype, and participate in the formation and accumulation of XFS aggregates within intra-and extra-ocular tissues.…”

Section: Risk Factors For Xfs and The Relation With Oxidation Stressmentioning

confidence: 99%

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Chiras

Kitsos

Petersen

et al. 2014

Critical Reviews in Clinical Laboratory Sciences

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Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.

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“…The effect of TGF-β on LOX expression was also confirmed by other researchers (van Meeteren and Ten Dijke, 2011). Tumor necrosis Factor-α (TNF-α) also stimulates LOX expression (Voloshenyuk et al, 2011b). It is interesting that our irradiation-surviving cells expressed higher IL6-(36.0-fold) and LOX-mRNA (4.8-fold) compared to un-irradiated parental cells in vitro (Nishioka et al, 2011).…”

Section: Introduction and Molecular Biology Of Loxmentioning

confidence: 95%

Lysyl Oxidase: From Basic Science to Future Cancer Treatment

Nishioka

Eustace

West

2012

Cell Struct. Funct.

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ABSTRACT. In this mini-review, we discuss the physiological and pathological roles of lysyl oxidase (LOX) and its family, LOX-like proteins (LOXL), in relation to prognosis of major cancers. The number of reports on LOX family is numerous. We have decided to review the articles that were recently published (i.e. past 5 years). Experimental techniques in molecular biology have advanced surprisingly in the past decade. Accordingly, the results of the studies are more reliable. Most studies reached the same conclusion; a higher LOX-or LOXLexpression is associated with a poor prognosis. Molecular experiments have already started aiming for clinical application, and the results are encouraging. Suppressing LOX or LOXL activities resulted in lower cell motility in collagen gel and, moreover, succeeded in reducing metastases in mice. LOX family members were originally recognized as molecules that cross-link collagen fibers in the extracellular matrix. Recent studies demonstrated that they are also involved in a phenomenon called Epithelial Mesenchymal Transition (EMT). This may affect cell movement and cancer cell invasiveness. LOX and LOXL2 are regulated by hypoxia, a major factor in the failure of cancer treatment. Here we discuss the molecular biology of the LOX family in relation to its role in tumor biology.

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TNF-α increases cardiac fibroblast lysyl oxidase expression through TGF-β and PI3Kinase signaling pathways

Cited by 74 publications

References 31 publications

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome

Lysyl Oxidase: From Basic Science to Future Cancer Treatment

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