LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2

Park, Jeongrak; Jang, Jin-Wook; Oh, Seo Jin; Kim, Min Hye; Shin, Chang Hun; Jeong, Min Seok; Heo, Kyun; Park, Jong Bae; Kim, Sang Ryong; Oh, Yong Seok

doi:10.1016/j.cellsig.2018.01.007

Cited by 32 publications

(27 citation statements)

References 58 publications

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“…Downstream of LPA receptor activation, the small GTPase Rho can be activated, subsequently activating Rho kinase [22,23] and leading to the formation of stress fibers and cell migration via inhibition of myosin light-chain phosphatase. These results strongly suggest that LPA signaling can affect cell migration, cell adhesion, and cell-to-cell junction formation [14,16,24,25].…”

Section: Discussionmentioning

confidence: 99%

KA-1002, a Novel Lysophosphatidic Acid Signaling Antagonist, Alleviates Bovine Tracheal Cell Disruption and Inflammation

Shin

Kim

et al. 2020

Animals

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The industrial livestock environment can cause stress and weakened immunity in cattle, leading to microbial infections which reduce productivity. As such, there is a need for an effective therapeutic agent that can alleviate uncontrolled destructive respiratory inflammation. We found that lysophosphatidic acid (LPA), a potent endogenous stress-induced inflammatory agent, causes respiratory tissue damage and triggers inflammation in bovine bronchial cells. LPA also inflames pulmonary bovine blood vessel cells to produce inflammatory cytokines. These findings strongly suggest that LPA is a highly important endogenous material exacerbating bovine respiratory diseases. We further identified a novel LPA-signaling antagonist, KA-1002, and showed that it alleviated LPA-mediated bovine tracheal cell disruption and inflammation. Therefore, KA-1002 could potentially serve as a novel therapeutic agent to maintain physiologically healthy and balanced conditions in bovine respiratory tracts.

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Section: Discussionmentioning

confidence: 99%

KA-1002, a Novel Lysophosphatidic Acid Signaling Antagonist, Alleviates Bovine Tracheal Cell Disruption and Inflammation

Shin

Kim

et al. 2020

Animals

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“…Little is known about the physiological functions of LPA 2 , but its signaling has been generally associated with cell survival and cell migration (Choi and Chun, 2013;Choi et al, 2010;Yung et al, 2015). Indeed, LPA 2 is involved with the invasion and metastasis of several type of cancer cells (Lee and Yun, 2010;Lopane et al, 2017;Park et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic acid receptor type 2 activation contributes to secondary damage after spinal cord injury in mice

López-Serrano

Santos-Nogueira

Francos-Quijorna

et al. 2019

Brain, Behavior, and Immunity

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Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions by signaling through six known G-protein-coupled receptors (LPA 1-LPA 6). In the central nervous system (CNS), LPA mediates a wide range of effects, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and contributions to pain, schizophrenia and hydrocephalus. We recently reported that LPA-LPA 1 signaling mediates functional deficits and myelin loss after spinal cord injury (SCI). Here, we provide clear evidence on the deleterious contribution of another LPA receptor, LPA 2 , to myelin loss after SCI. We found that LPA 2 is constitutively expressed in the spinal cord parenchyma and its transcripts were up-regulated after contusion injury, in part, by microglial cells. We also found that the demyelinating lesion triggered by intraspinal injection of LPA into the undamaged spinal cord was markedly reduced in the lack of LPA 2. Similarly, LPA 2 deficient mice showed enhanced motor skills and myelin sparing after SCI. To gain insights into the detrimental actions of LPA 2 in spinal cord we performed cell culture studies. These experiments revealed that, similar to LPA 1 , activation of microglia LPA 2 led to oligodendrocyte cell death. Moreover, we also found that the cytotoxic effects underlaying microglial LPA-LPA 2 axis were mediated by the release of purines by microglia and the activation of P 2 X 7 receptor on oligodendrocytes. Overall, this study provides new mechanistic insights into how LPA contributes to SCI physiopathology, and suggest that targeting LPA 2 could be a novel therapeutic approach for the treatment of acute SCI.

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“…The specific manifestation is that overexpression of TRIP6 enhanced the LPA-induced cell migration, while in contrast, inhibition of TRIP6 expression suppressed the LPAinduced cell migration, suggesting that TRIP6 may mediate the LPA2-induced cancer cell migration (96). Park et al found that LPA could activate the downstream Ga 12/13/RhoA signaling pathway through LPA 1/2 receptor to induce the phosphorylation of ERM proteins (Ezrin/Radixin/Moesin), which promotes the metastasis of ovarian cancer cell line OVC-3 (97).…”

Section: Lysophosphatidic Acid Receptor (Lpar)mentioning

confidence: 99%

Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer

Shen²,

et al. 2020

Front. Oncol.

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Ovarian cancer is one of the most malignant gynecological cancers around the world. In spite of multiple treatment options, the five-year survival rate is still very low. Several metabolism alterations are described as a hallmark in cancers, but alterations of lipid metabolism in ovarian cancer have been paid less attention. To explore new markers/targets for accurate diagnosis, prognosis, and therapeutic treatments based on metabolic enzyme inhibitors, here, we reviewed available literature and summarized several key metabolic enzymes in lipid metabolism of ovarian cancer. In this review, the rate limiting enzymes associated with fatty acid synthesis (FASN, ACC, ACLY, SCD), the lipid degradation related enzymes (MAGL, CPT, 5-LO, COX2), and the receptors related to lipid uptake (FABP4, CD36, LDLR), which promote the development of ovarian cancer, were analyzed and evaluated. We also focused on the review of application of current metabolic enzyme inhibitors for the treatment of ovarian cancer through which the potential therapeutic agents may be developed for ovarian cancer therapy.

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LPA-induced migration of ovarian cancer cells requires activation of ERM proteins via LPA1 and LPA2

Cited by 32 publications

References 58 publications

KA-1002, a Novel Lysophosphatidic Acid Signaling Antagonist, Alleviates Bovine Tracheal Cell Disruption and Inflammation

KA-1002, a Novel Lysophosphatidic Acid Signaling Antagonist, Alleviates Bovine Tracheal Cell Disruption and Inflammation

Lysophosphatidic acid receptor type 2 activation contributes to secondary damage after spinal cord injury in mice

Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer

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