Phospholipase signalling networks in cancer

Park, Jong Bae; Lee, Chang Sup; Jang, Jin-Wook; Ghim, Jaewang; Kim, Youn‐Jae; You, Sungyoung; Hwang, Daehee; Suh, Pann‐Ghill; Ryu, Sung Ho

doi:10.1038/nrc3379

Cited by 219 publications

(167 citation statements)

References 136 publications

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“…Recently, Campos et al (69) reported that hBMSCs stimulated by proinflammatory cytokines had enhanced levels of 20:4n-6-containing PC species 38:4. The 20:4n-6 signaling also has a pronounced role in tumor cells, which have high expression levels of PLA 2 s and COX-2, and enhanced production of PGE2 (70,71). Differentiation-related increase of GPL species with 20:4n-6 was recently found in cultured neural stem cells (72).…”

Section: Discussionmentioning

confidence: 99%

Metabolism and phospholipid assembly of polyunsaturated fatty acids in human bone marrow mesenchymal stromal cells

Tigistu-Sahle

Lampinen

Kilpinen

et al. 2017

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Metabolism and phospholipid assembly of polyunsaturated fatty acids in human bone marrow mesenchymal stromal cells

Tigistu-Sahle

Lampinen

Kilpinen

et al. 2017

Journal of Lipid Research

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“…Thus, these data support a role of Pla2g16 in tumorigenesis in vivo. Although Pla2g16-null mice or mice with mutations in other phospholipases are not cancer-prone, many of these mice decrease tumor progression when combined with other oncogenic defects (49). Crosses of Pla2g16 mice with p53 mutant mice will be invaluable in deciphering the in vivo role of Pla2g16 in metastasis.…”

Section: Discussionmentioning

confidence: 99%

Pla2g16 phospholipase mediates gain-of-function activities of mutant p53

Xiong¹,

Tu²,

Kollareddy

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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p53 R172H/+ mice inherit a p53 mutation found in Li-Fraumeni syndrome and develop metastatic tumors at much higher frequency than p53 +/− mice. To explore the mutant p53 metastatic phenotype, we used expression arrays to compare primary osteosarcomas from p53 R172H/+ mice with metastasis to osteosarcomas from p53 +/− mice lacking metastasis. For this study, 213 genes were differentially expressed with a P value <0.05. Of particular interest, Pla2g16, which encodes a phospholipase that catalyzes phosphatidic acid into lysophosphatidic acid and free fatty acid (both implicated in metastasis), was increased in p53 R172H/+ osteosarcomas. Functional analyses showed that Pla2g16 knockdown decreased migration and invasion in mutant p53-expressing cells, and vice versa: overexpression of Pla2g16 increased the invasion of p53-null cells. Furthermore, Pla2g16 levels were increased upon expression of mutant p53 in both mouse and human osteosarcoma cell lines, indicating that Pla2g16 is a downstream target of the mutant p53 protein. ChIP analysis revealed that several mutant p53 proteins bind the Pla2g16 promoter at E26 transformationspecific (ETS) binding motifs and knockdown of ETS2 suppressed mutant p53 induction of Pla2g16. Thus, our study identifies a phospholipase as a transcriptional target of mutant p53 that is required for metastasis. mammary tumor | fatty acid metabolism T he p53 tumor suppressor pathway is inactivated in ∼50% of human cancers (http://p53.iarc.fr). Missense mutations in particular account for 80% of p53 alterations, suggesting that mutant p53 proteins provide additional advantages for tumor cell growth (1). Li-Fraumeni syndrome patients with p53 missense mutations have a higher cancer incidence and an earlier age of tumor onset than individuals with truncating or splicing mutations (2). p53 knockin mice show a gain-of-function (GOF) phenotype in vivo, with high metastatic capacity compared with mice inheriting a p53-null allele (3, 4). GOF activities of mutant p53 are mediated by suppression of the p53 family members, p63 and p73 (3-6). Other mechanisms of mutant p53 GOF include mutant-p53 complexes with Smad that fuel TGF-β-induced metastasis (7) and integrin recycling (8). Additionally, mutant p53 interacts with the vitamin D receptor and converts vitamin D into an antiapoptotic agent (9-14). More recently, mutant p53 was reported to form transcriptional complexes on promoters of genes encoding several enzymes of the Mevalonate pathway, which increases metastasis of breast cancer cells (9). These data suggest multiple pathways contribute to the GOF phenotypes of cells with mutant p53. Although mutant p53 lacks sequencespecific DNA binding activity, its interaction with other transcriptional factors or the components of basic transcriptional machinery allow it to modulate gene expression (15). ChIP-onchip and ChIP-sequencing techniques show that mutant p53 affects transcription of many genes (9, 13, 16, 17).In this study, expression array analyses identified gene differences between p53 R172H/+ m...

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“…Many reports have concluded that PLD2 is critically linked to the signals that mediate the processes involved tumorigenesis (transformation and tumor growth) and metastasis (Park et al, 2012). SOS, which activates the Ras-MAPK cascade, can be recruited to the plasma membrane by PLD2-derived PA generation, and eventually, MAPK signaling increases cell proliferation and transformation in NIH-3T3 cells (Zhao et al, 2007).…”

Section: Notementioning

confidence: 99%

“…PLD2 can be activated by multiple extracellular ligands and the major roles of PLD2 can be achieved by PA generation. PA is considered as a second messenger that mediates a variety of cellular functions such as, proliferation, cell growth, vesicle trafficking (endocytosis and exocytosis), and actin-cytoskeletal arrangement (Park et al, 2012). Furthermore, animal studies have shown that PLD2 can serve as a key mediator of in vivo pathophysiologic functions (Oliveira et al, 2010).…”

Section: Functionmentioning

confidence: 99%

“…Interacting partners include various classes of proteins (kinase, phosphatase, GTPase, structural protein, transporter, adapter, phospholipase, transcription factor), and phospholipids (PA, PtdIns5P, PtdIns(4,5)P 2 , and PtdIns(3,4,5)P 3 ). Proliferative signaling Multiple extracellular mitogenic signals, such as, EGF, platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) can activate PLD2 to generate PA Park et al, 2012). Specially, PLD2 is known to be implicated in EGFmediated cell proliferation (Ahn et al, 2003).…”

Section: Functionmentioning

confidence: 99%

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