Abnormal production of the TNF-homologue APRIL increases the proliferation of human malignant glioblastoma cell lines via a specific receptor

Deshayes, Frédérique; Laprée, Geneviève; Portier, A; Richard, Yolande; Pencalet, Philippe; Michelet, Dominique; Horellou, Philippe; Tsapis, Andréas

doi:10.1038/sj.onc.1207350

Cited by 55 publications

(49 citation statements)

References 26 publications

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“…5). APRIL is also thought to promote tumor formation in a number of solid malignancies, either indirectly via infiltrating cells or directly via autocrine stimulation of the tumor itself (1,6,7). In line with these results, we recently identified a clear role for APRIL in supporting tumorigenesis in the gastrointestinal tract (8).…”

supporting

confidence: 55%

“…Computational Design of Selective Variants-X-ray crystal structures of the extracellular domain (ECD) 6 of murine APRIL in complex with the ECD of human TACI (Protein Data Bank entry 1xu1) and the ECD of human BCMA (Protein Data Bank 1xu2) have been solved at a resolution of 1.9 and 2.35 Å, respectively (21). Computational design of receptor selective mutants was performed as described previously (22,23,26).…”

Section: Methodsmentioning

confidence: 99%

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The Design and Characterization of Receptor-selective APRIL Variants

Kimberley¹,

Sloot

Guadagnoli³

et al. 2012

Journal of Biological Chemistry

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Background: APRIL binds two receptors, BCMA and TACI, so separating signaling outcomes is difficult. Results: We used an algorithm to design a variant of APRIL that specifically binds BCMA and two variants that selectively bind TACI. Conclusion: TACI and BCMA signals differ in the context of B cell stimulation. Significance: These variants will help decipher APRIL signaling in physiology and disease settings.

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supporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

The Design and Characterization of Receptor-selective APRIL Variants

Kimberley¹,

Sloot

Guadagnoli³

et al. 2012

Journal of Biological Chemistry

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“…APRIL is expressed by a subset of immune cells that also produce B-cell activating factor (BAFF): monocytes, macrophages, (Hahne et al, 1998;Nardelli et al, 2001;He et al, 2004;Chu et al, 2007) as well as in some non-immune cells such as epithelial cells and osteoclasts. Moreover, PRIL is abundantly expressed in a variety of tumor cells and tissues, such as lung carcinomas, melanoma (Roth et al, 2001;Stein et al, 2002), lymphoid malignancies (Nardelli et al, 2001;Deshayes et al, 2004;Kern et al, 2004;Moreaux et al, 2004;Chiu et al, 2007;Pelekanou et al, 2008;Yaccoby et al, 2008) and in particular gastrointestinal tumors including rectum, duodenum, colon, stomach and esophagus (Hahne et al, 1998;Kelly et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of a Proliferation-inducing Ligand (PRIL) Suppresses the Proliferation of Gastric Cancer Cells

Cui

Li²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Asian Pacific J Cancer Prev, 13, 633-636 IntroductionGastric cancer (GC), the second most common cause of cancer-related death in the world, can develop in any part of the stomach and spread throughout the stomach and to other organs. There are about 1,000,000 new diagnoses and 800,000 deaths worldwide each year (Kamangar et al., 2006). The 5-year survival rate for curative surgical resection ranges from 30-50% for patients with stage II disease and from 10-25% for patients with stage III disease. The operative mortality rate for patients undergoing curative surgical resection at major academic centers is less than 3% (http://emedicine.medscape.com/ article/278744-overview). In this scenario, understanding the molecular mechanisms underlying the initiation and progression of GC is important for prevention, early diagnosis and identifying novel therapeutic and clinical targets for GC (Li et al., 2009;Yu et al., 2009).A proliferation-inducing ligand (PRIL) (also known as TALL-2, TRDL1, or TNFSF13) is a member of tumor necrosis factor (TNF) family. It was originally identified in cell lines and primary samples from various tumor lesions in 1998 and named for its capacity to stimulate the proliferation of tumor cells (Hahne et al., 1998). In contrast to most TNF family members, APRIL is processed in the Golgi apparatus into the active soluble form by a furin convertase (Lopez-Fraga et al., 2001). APRIL is expressed by a subset of immune cells that also produce B-cell activating factor (BAFF): monocytes, macrophages, Moreover, the cell cycle was arrested at G2/M phase, elucidating the mechanism underlying the inhibitory effect of siRNA on cell proliferation. Conclusions: Our study indicated that PRIL functions in promoting cell growth, and lentivirus-mediated PRIL gene knockdown might be a promising strategy in the treatment of gastric cancer.

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“…APRIL and BAFF (TNFSF13B) (3) bind to two receptors (4-7), BCMA (TNRSF17) (8,9) and TACI (TNFRSF13B) (10), but with a different affinity (11)(12)(13); BAFF also binds to its specific receptor, BAFFR (TNFRSF13C) (14,15). APRIL has been reported to bind also the proteoglycan syndecan-1 (CD138) (16,17), and a not-yet-identified APRIL receptor has been advanced, as well (18,19). This complex system of two ligands and (at least) three receptors was considered exclusive to B lymphocytes; however, recently, all or some of these five molecules have been identified in mesenchymal cells (20), normal tissues (20)(21)(22)(23)(24), and epithelial tumors (20,21,(24)(25)(26), suggesting additional non-immune cellrelated functions for these ligands and receptors, in both physiological and malignant tissues.…”

mentioning

confidence: 99%

APRIL Binding to BCMA Activates a JNK2–FOXO3–GADD45 Pathway and Induces a G2/M Cell Growth Arrest in Liver Cells

Notas

Alexaki

Kampa

et al. 2012

The Journal of Immunology

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The TNF superfamily ligands APRIL and BAFF bind with different affinity to two receptors, BCMA and TACI, and induce cell survival and/or proliferation, whereas BAFF also binds specifically to BAFFR. These molecules were considered specific for the immune system. Recently, however, they were also found in epithelial and mesenchymal noncancerous and cancerous tissues and cell lines. In this article, we report that hepatocellular carcinoma (HCC) cell lines HepG2 and Hep3B and HCC specimens express APRIL and BAFF and their receptors BCMA and BAFFR, but not TACI; APRIL/BCMA is enhanced in HCC, compared with normal liver tissue. In contrast to previous reports, APRIL binding to BCMA decreases cell proliferation by inducing G2/M cell cycle arrest, whereas BAFF has no effect on cell growth. HCC cells therefore represent a rare system in which these two ligands (APRIL and BAFF) exert a differential effect and may serve as a model for specific APRIL/BCMA actions. We show that the effect of APRIL is mediated via BCMA, which does not activate the classical NF-κB pathway, whereas it induces a novel signaling pathway, which involves JNK2 phosphorylation, FOXO3A activation, and GADD45 transcription. In addition, JNK2 mediates the phosphorylation of Akt, which is activated but does not participate in the antiproliferative effect of APRIL. Furthermore, transcriptome analysis revealed that APRIL modifies genes specifically related to cell cycle modulation, including MCM2/4/5/6, CDC6, PCNA, and POLE2. Our data, therefore, identify a novel APRIL/BCMA signaling pathway in HCC and suggest that APRIL could have a pleiotropic role in tumor biology.

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Abnormal production of the TNF-homologue APRIL increases the proliferation of human malignant glioblastoma cell lines via a specific receptor

Cited by 55 publications

References 26 publications

The Design and Characterization of Receptor-selective APRIL Variants

The Design and Characterization of Receptor-selective APRIL Variants

Knockdown of a Proliferation-inducing Ligand (PRIL) Suppresses the Proliferation of Gastric Cancer Cells

APRIL Binding to BCMA Activates a JNK2–FOXO3–GADD45 Pathway and Induces a G2/M Cell Growth Arrest in Liver Cells

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