Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer

Yun, C. Chris

doi:10.3390/cancers11070958

Cited by 22 publications

(26 citation statements)

References 183 publications

(249 reference statements)

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“…18 Changes in LPL metabolism have been found to induce inflammatory responses, apoptosis, cell proliferation, disruptions in mitochondrial functions, and other cellular responses. [19][20][21][22][23] Studies conducted on changes in LPL levels' modulations post-CNS injury suggest that altered LPL production and degradation can disrupt the nervous system and result in neurologic disorders. [24][25][26] Previous studies have investigated the role of LPLs in regulating aqueous humor outflow and IOP, 27 mechanisms that are impaired in glaucoma, but there is still little knowledge about the role of LPLs in the ON.…”

mentioning

confidence: 99%

Alteration in Lysophospholipids and Converting Enzymes in Glaucomatous Optic Nerves

Milbeck

Bhattacharya

2020

Invest. Ophthalmol. Vis. Sci.

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To determine whether lysophospholipid (LPL) profiles and corresponding conversion enzymes in the LPL pathways are altered in the optic nerve (ON) between human control and glaucoma samples. METHODS. Lipids extracted from control (n = 11) and glaucomatous (n = 12) ON samples using the Bligh and Dyer method were subjected to high-resolution mass spectrometry on a Q-exactive mass spectrometer coupled with a high-performance liquid chromatography (Accela 600) system. Analysis was performed for LPLs (lysophosphatidylcholines, lysophosphatidylserines, lysophosphatidylethanolamines, lysophosphatidylinositols, and lysosphingomyelines) using LipidSearch v.4.1, MZmine v.2.0, and MetaboAnalyst v.4.0. LPL synthesis and degradation pathway maps, utilizing UniProt and BRENDA database entries as needed, were created using Kyoto Encyclopedia of Genes and Genomes (KEGG)-based tools. The mRNA expression level in normal and glaucomatous human ON were analyzed using Gene Expression Omnibus (GEO) entry GSE45570. Protein amounts were determined using PHAST gel and dot blot and were used for normalization of protein amounts across samples. Western blot, ELISA, and protein quantification were performed using established protocols. RESULTS. Principal component analysis of ON LPL profile placed control and glaucomatous ONs in two distinct separate groups. Mass spectrometric analysis of ON revealed decrease in lysophosphatidic acid, lysophosphatidylethanolamine, lysophosphatidylcholine, and significant increase in diacylglycerol in glaucomatous ON. Statistical analysis of LPL conversion enzymes revealed significant overexpression of phosphatidate phosphatase LPIN2, phospholipid phosphatase 3, phosphatidylcholine-sterol acyltransferase, and calcium-dependent phospholipase 2, and significant downregulation of glycerol-3-phosphate acyltransferase 4 at mRNA level in glaucomatous ON. Western blot and ELISA confirmed proteomic differences between normal and diseased ON. CONCLUSIONS. Our analysis revealed alterations in specific LPL levels and corresponding select enzyme-level changes in glaucomatous ON.

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confidence: 99%

Alteration in Lysophospholipids and Converting Enzymes in Glaucomatous Optic Nerves

Milbeck

Bhattacharya

2020

Invest. Ophthalmol. Vis. Sci.

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“…Autotoxin is an ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) family member which produces LPA. Up-regulated in most of the metastatic cancers, autotoxin was also associated with invasiveness and aggressive metastatic potential of cancers and was positively correlated to tumour angiogenesis in colorectal cancer [ 38 ]. Furthermore, evidence has identified autotoxins as secretory proteins in human melanoma cells, and the overexpression of autotoxins was co-relatable to increased motility and invasiveness [ 39 ].…”

Section: Lpa5 Is a Friend In Need Among Gpcrsmentioning

confidence: 99%

Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT

Gundamaraju

Azimi

et al. 2020

Biomedicines

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The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

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“…S1P has been implicated in both physiological and pathological neovascularization, as detailed in the next section. Numerous human gene analysis and preclinical studies have investigated the roles of LPA and LPA receptors [68,69]. These studies have shown that LPA is essential for vascularization [70].…”

Section: Sphingolipids In Ocular Neovascularizationmentioning

confidence: 99%

“…Numerous human gene analysis and preclinical studies have investigated the roles of LPA and LPA receptors [ 68 , 69 ]. These studies have shown that LPA is essential for vascularization [ 70 ].…”

Section: Glycerophospholipids In Ocular Neovascularizationmentioning

confidence: 99%

Lipid Signaling in Ocular Neovascularization

Terao

Kaneko

2020

IJMS

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Vasculogenesis and angiogenesis play a crucial role in embryonic development. Pathological neovascularization in ocular tissues can lead to vision-threatening vascular diseases, including proliferative diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, choroidal neovascularization, and corneal neovascularization. Neovascularization involves various cellular processes and signaling pathways and is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF). Modulating these circuits may represent a promising strategy to treat ocular neovascular diseases. Lipid mediators derived from membrane lipids are abundantly present in most tissues and exert a wide range of biological functions by regulating various signaling pathways. In particular, glycerophospholipids, sphingolipids, and polyunsaturated fatty acids exert potent pro-angiogenic or anti-angiogenic effects, according to the findings of numerous preclinical and clinical studies. In this review, we summarize the current knowledge regarding the regulation of ocular neovascularization by lipid mediators and their metabolites. A better understanding of the effects of lipid signaling in neovascularization may provide novel therapeutic strategies to treat ocular neovascular diseases and other human disorders.

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Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer

Cited by 22 publications

References 183 publications

Alteration in Lysophospholipids and Converting Enzymes in Glaucomatous Optic Nerves

Alteration in Lysophospholipids and Converting Enzymes in Glaucomatous Optic Nerves

Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT

Lipid Signaling in Ocular Neovascularization

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