Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development

Valdés-Rives, Silvia Anahi; González-Arenas, Aliesha

doi:10.1155/2017/9173090

Cited by 87 publications

(97 citation statements)

References 141 publications

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“…Previous studies have described a role for LPA and autotaxin, its main synthetic enzyme, in inflammatory processes (8,25,43,45). In line with this, we found that expression of LPA1 was To understand how LPA1 exerts its influence on the inflammatory component of MS and EAE, we examined infiltration and activation of immune cells.…”

Section: Discussionsupporting

confidence: 78%

“…In the past years, the role of LPA in the pathogenesis of different immune-related diseases has been recognized. LPA dysregulation has been implicated in different inflammatory diseases, such as atherosclerosis (8), cancer (45), and MS (41) because of its effect on immune cells, of both the innate and adaptive immune systems (3,15,23). However, despite the growing knowledge in this field, many aspects of the role of LPA in immune-related pathogenesis remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Activation of macrophages by lysophosphatidic acid through the lysophosphatidic acid receptor 1 as a novel mechanism in multiple sclerosis pathogenesis

Fransson

Gómez

Romero-Imbroda

et al. 2019

Preprint

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Multiple sclerosis (MS) is a neuro-inflammatory disease for which the pathogenesis remains largely unclear. Lysophosphatidic acid (LPA) is an endogenous phospholipid that is involved in multiple immune cell functions and is dysregulated in MS. Its receptor LPA1 is expressed in macrophages and regulates their activation, which is of interest due to the role of macrophage activation in MS in both destruction and repair.In this study, we studied the viable Malaga variant of LPA1-null mutation as well as pharmaceutical inhibition of LPA1 in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. LPA1 expression was also analyzed in both wild-type EAE mice and MS patient immune cells. The effect of LPA and LPA1 on macrophage activation was studied in human monocyte-derived macrophages.We show that lack of LPA1 activity induces a milder clinical course in EAE, and that Lpar1 expression in peripheral blood mononuclear cells (PBMCs) correlates with onset of relapses and severity in wild-type EAE mice. We see the same over-expression in PBMCs from MS patients during relapse compared to progressive forms of the disease, and in monocyte-derived macrophages after exposure to pro-inflammatory stimuli. In addition, LPA induced a proinflammatory-like response in macrophages through LPA1, providing a plausible way in which LPA and LPA1 dysregulation can lead to the inflammation seen in MS.These data show a new mechanism of LPA signaling in the pathogenesis of MS, prompting further research into its use as a therapeutic target biomarker.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Activation of macrophages by lysophosphatidic acid through the lysophosphatidic acid receptor 1 as a novel mechanism in multiple sclerosis pathogenesis

Fransson

Gómez

Romero-Imbroda

et al. 2019

Preprint

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“…LPA is a bioactive phospholipid that stimulates the proliferation, migration, and survival of many cell types [24]. LPA has no membrane-perturbing effects and is water-soluble [25].…”

Section: Physiological Functions Of the Lpa-atx Axismentioning

confidence: 99%

Role of autotaxin in cancer stem cells

Lee

Suh

Lee

et al. 2018

Cancer Metastasis Rev

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Stem cells are a rare subpopulation defined by the potential to self-renew and differentiate into specific cell types. A population of stem-like cells has been reported to possess the ability of self-renewal, invasion, metastasis, and engraftment of distant tissues. This unique cell subpopulation has been designated as cancer stem cells (CSC). CSC were first identified in leukemia, and the contributions of CSC to cancer progression have been reported in many different types of cancers. The cancer stem cell hypothesis attempts to explain tumor cell heterogeneity based on the existence of stem cell-like cells within solid tumors. The elimination of CSC is challenging for most human cancer types due to their heightened genetic instability and increased drug resistance. To combat these inherent abilities of CSC, multi-pronged strategies aimed at multiple aspects of CSC biology are increasingly being recognized as essential for a cure. One of the most challenging aspects of cancer biology is overcoming the chemotherapeutic resistance in CSC. Here, we provide an overview of autotaxin (ATX), lysophosphatidic acid (LPA), and their signaling pathways in CSC. Increasing evidence supports the role of ATX and LPA in cancer progression, metastasis, and therapeutic resistance. Several studies have demonstrated the ATX-LPA axis signaling in different cancers. This lipid mediator regulatory system is a novel potential therapeutic target in CSC. In this review, we summarize the evidence linking ATX-LPA signaling to CSC and its impact on cancer progression and metastasis. We also provide evidence for the efficacy of cancer therapy involving the pharmacological inhibition of this signaling pathway.

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“…Recently, LPA 1 receptor was discovered related to the proliferation and migration of GBM. In three GBM cell lines, LPA induces PKCα activation by LPA 1 , leading to nuclear translocation of kinases, increasing cell number and increasing cell viability [85,86].…”

Section: Lpar and Glioblastomamentioning

confidence: 99%

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

Xiang¹,

Lü²,

Shao³

et al. 2020

J. Cancer

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Lysophosphatidic acid (LPA, 1-acyl-2-hemolytic-sn-glycerol-3-phosphate) extracted from membrane phospholipid is a kind of simple bioactive glycophospholipid, which has many biological functions such as stimulating cell multiplication, cytoskeleton recombination, cell survival, drug-fast, synthesis of DNA and ion transport. Current studies have shown that six G-coupled protein receptors (LPAR1-6) can be activated by LPA. They stimulate a variety of signal transduction pathways through heterotrimeric G-proteins (such as Gα12/13, Gαq/11, Gαi/o and GαS). LPA and its receptors play vital roles in cancers, nervous system diseases, cardiovascular diseases, liver diseases, metabolic diseases, etc. In this article, we discussed the structure of LPA receptors and elucidated their functions in various diseases, in order to better understand them and point out new therapeutic schemes for them.

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Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development

Cited by 87 publications

References 141 publications

Activation of macrophages by lysophosphatidic acid through the lysophosphatidic acid receptor 1 as a novel mechanism in multiple sclerosis pathogenesis

Activation of macrophages by lysophosphatidic acid through the lysophosphatidic acid receptor 1 as a novel mechanism in multiple sclerosis pathogenesis

Role of autotaxin in cancer stem cells

Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases

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