H-REV107-1 Stimulates Growth in Non-Small Cell Lung Carcinomas via the Activation of Mitogenic Signaling

Nazarenko, Irina; Kristiansen, Glen; Fonfara, Sabine; Guenther, R.; Gieseler, Cornelia; Kemmner, Wolfgang; Schäfer, Reinhold; Petersen, Iver; Sers, Christine

doi:10.2353/ajpath.2006.051341

Cited by 24 publications

(29 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PLA 2 has been reported to function in adipocyte cell signaling (22,23), differentiation (3-7), and in the regulation of important adipocyte metabolic processes such as lipolysis and glucose transport (8 -11). Because dysregulated adipocyte differentiation and metabolism are linked to obesity and associated pathologies, understanding phospholipid metabolism in adipose tissue is critical.…”

Section: Resultsmentioning

confidence: 99%

Identification and Functional Characterization of Adipose-specific Phospholipase A2 (AdPLA)

Duncan¹,

Sarkadi-Nagy²,

Jaworski

et al. 2008

Journal of Biological Chemistry

146

151

View full text Add to dashboard Cite

Phospholipases A 2 (PLA 2 s) catalyze hydrolysis of fatty acids from the sn-2 position of phospholipids. Here we report the identification and characterization of a membrane-associated intracellular calcium-dependent, adipose-specific PLA 2 that we named AdPLA (adipose-specific phospholipase A 2 ). We found that AdPLA was highly expressed specifically in white adipose tissue and was induced during preadipocyte differentiation into adipocytes. Clearance of AdPLA by immunoprecipitation significantly decreased PLA activity in white adipose tissue lysates but had no effect on liver lysates, where expression was hardly detectable. In characterizing AdPLA, we employed radiochemical assays with TLC analysis of the enzyme activity of lysates from COS-7 cells overexpressing AdPLA. For kinetic studies, we produced purified recombinant AdPLA for use in a lipoxidasecoupled spectrophotometric assay. AdPLA generated free fatty acid and lysophospholipid from phosphatidylcholine with a preference for hydrolysis at the sn-2 position. Although we found low but detectable lysophospholipase activity, AdPLA showed no significant activity against a variety of other lipid substrates. Calcium was found to activate AdPLA but was not essential for activity. Studies with known phospholipase inhibitors, including bromoenolactone, methyl arachidonyl fluorophosphate, AACOCF 3 , 7,7-dimethyl-5,8-eicosadienoic acid, and thioetheramide, supported that AdPLA is a phospholipase. Mutational studies showed that His-23 and Cys-113 are critical for activity of AdPLA and suggested that AdPLA is likely a His/ Cys PLA 2 . Overall, although AdPLA is similar to other histidine phospholipases in pH and calcium dependence, AdPLA showed different characteristics in many regards, including predicted catalytic mechanism. AdPLA may therefore represent the first member of a new group of PLA 2 s, group XVI.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification and Functional Characterization of Adipose-specific Phospholipase A2 (AdPLA)

Duncan¹,

Sarkadi-Nagy²,

Jaworski

et al. 2008

Journal of Biological Chemistry

146

151

View full text Add to dashboard Cite

show abstract

“…Nuclear targeted H-REV107 has been shown to stimulate cell growth of non-small cell lung carcinomas [48]. In contrast, nuclear targeted H-REV107 111–123 and RIG1 111–123 peptides induce profound proapoptotic activities in cancer cells [12,49].…”

Section: Discussionmentioning

confidence: 99%

H-rev107 regulates prostaglandin D2 synthase-mediated suppression of cellular invasion in testicular cancer cells

Shyu

Wang

et al. 2013

J Biomed Sci

View full text Add to dashboard Cite

BackgroundH-rev107 is a member of the HREV107 type II tumor suppressor gene family which includes H-REV107, RIG1, and HRASLS. H-REV107 has been shown to express at high levels in differentiated tissues of post-meiotic testicular germ cells. Prostaglandin D2 (PGD2) is conjectured to induce SRY-related high-mobility group box 9 (SOX9) expression and subsequent Sertoli cell differentiation. To date, the function of H-rev107 in differentiated testicular cells has not been well defined.ResultsIn the study, we found that H-rev107 was co-localized with prostaglandin D2 synthase (PTGDS) and enhanced the activity of PTGDS, resulting in increase of PGD2 production in testis cells. Furthermore, when H-rev107 was expressed in human NT2/D1 testicular cancer cells, cell migration and invasion were inhibited. Also, silencing of PTGDS would reduce H-rev107-mediated increase in PGD2, cAMP, and SOX9. Silencing of PTGDS or SOX9 also alleviated H-rev107-mediated suppression of cell migration and invasion.ConclusionsThese results revealed that H-rev107, through PTGDS, suppressed cell migration and invasion. Our data suggest that the PGD2-cAMP-SOX9 signal pathway might play an important role in H-rev107-mediated cancer cell invasion in testes.

show abstract

“…However, Pla2g16 was also labeled an oncogene because it increases proliferation of nonsmall-cell lung cancer cells and its overexpression correlates with a poor prognosis (25). Functionally, Pla2g16 is a member of the phospholipase family of small lipases that exhibit diverse functions, including digestion of dietary phospholipids and cell signaling (Fig.…”

mentioning

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.

View full text Add to dashboard Cite

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...

show abstract

H-REV107-1 Stimulates Growth in Non-Small Cell Lung Carcinomas via the Activation of Mitogenic Signaling

Cited by 24 publications

References 47 publications

Identification and Functional Characterization of Adipose-specific Phospholipase A2 (AdPLA)

Identification and Functional Characterization of Adipose-specific Phospholipase A2 (AdPLA)

H-rev107 regulates prostaglandin D2 synthase-mediated suppression of cellular invasion in testicular cancer cells

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

Contact Info

Product

Resources

About